Last Modified: November 1, 2001
Table of Contents
CancerMail from the National Cancer Institute
UI - 21096273
AU - Chebotarev AN; Kirichenko OP; Sokolova OI
TI - Quantitative estimation of chromosome aberration frequency in cancer patients induced by endogenous and exogenous factors.
SO - Bull Exp Biol Med 2000 Nov;130(11):1106-8
AD - Medical Genetic Research Center, Russian Academy of Medical Sciences, Moscow, Russia.
In patients with skin melanoma and colon cancer, cell distribution by the number of chromosome aberrations cannot be described by Poisson distribution, but corresponds to a bipopulation model combining the Poisson and geometric distributions. In contrast to the control, in patients with malignant tumors, cells with geometric distribution possess the majority of chromosomal aberrations.
UI - 21274924
AU - Sanz Esponera J
TI - [Genetic alterations in the differential diagnosis of melanocytic diseases]
SO - An R Acad Nac Med (Madr) 2000;117(4):815-24
The biological significance of melanocytic lesions depends on its association with melanomas. Some melanocytic lesions are considered as precursors of melanoma while others may share histological similarities with malignant lesions. Melanomas exhibit clinical, epidemiological and histological heterogeneity. Molecular and cytogenetic studies may supply additional information to supplement the histopathological evaluation. Several genes have been linked to melanomas: CMM1 on chromosome 1p36 and CMM2 on 9p21, and other chromosomal regions where tumor suppressor genes are located as p16 (9p21) and p53 (17p13). We analyzed different melanocytic lesions to determine LOH at 9p21 and 17p13 and to assess clonality by the HUMARA technique. All the malignant melanomas were monoclonal and all the benignant lesions we analyzed were policlonal in our series including deep penetrating nevi and Spitz Nevi. LOH at 9p21 was determined in 60% melanomas, 50% Spitz and 0% intradermal nevi. In conclusion, genotypic changes may supplement the phenotypic or morphological evaluation of melanocytic lesions.
UI - 21392454
AU - Krygier G; Lombardo K; Vargas C; Alvez I; Costa R; Ros M; Echenique M; Navarro V; Delgado L; Viola A; Muse A
TI - Familial uveal melanoma: report on three sibling cases.
SO - Br J Ophthalmol 2001 Aug;85(8):1007-8
UI - 21388213
AU - Brem R; Hildebrandt T; Jarsch M; Van Muijen GN; Weidle UH
TI - Identification of metastasis-associated genes by transcriptional profiling of a metastasizing versus a non-metastasizing human melanoma cell line.
SO - Anticancer Res 2001 May-Jun;21(3B):1731-40
AD - Roche Pharma Research, Basel, Switzerland.
In order to identify genes associated with the metastatic phenotype we have compared the expression pattern of 6800 genes in a metastatic (NMCL-1) versus a non-metastatic (530) human melanoma cell line making use of DNA microarrays. The differentially expressed genes identified are involved in control of transcription, regulation of the cell-cycle, proteolysis, cell adhesion, immune response and signaling. A remarkable feature of the system under investigation is the consistent down-regulation of MHC-related and cell adhesion mediating genes in the metastatic cell line.
UI - 21397938
AU - Polsky D; Young AZ; Busam KJ; Alani RM
TI - The transcriptional repressor of p16/Ink4a, Id1, is up-regulated in early melanomas.
SO - Cancer Res 2001 Aug 15;61(16):6008-11
AD - Oncology Center, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231-1000, USA.
The helix-loop-helix transcription factor Id1 coordinates cell growth and differentiation pathways within mammalian cells and has been implicated in regulating G(1)-S phase cell cycle transitions. Recently Id1 has been shown to repress Ets- and E-protein-mediated transactivation of p16/Ink4a. Because the p16/Ink4a protein has been demonstrated to be inactivated in subsets of familial and sporadic melanomas, we sought to determine whether Id1 regulation of p16/Ink4a expression might be involved in the development of this human tumor. Here we evaluate 21 melanocytic lesions at various stages of malignant progression from common melanocytic nevi to metastatic melanomas and examine these lesions for Id1 and p16/Ink4a expression. We demonstrate that Id1 expression correlates with loss of p16/Ink4a expression in melanoma in situ; however, more advanced stages of melanoma do not express Id1 except within perivascular regions, despite overall decreased p16/Ink4a expression in these lesions. Microdissected lesions were evaluated for p16/Ink4a sequence, and invasive melanomas that did not express Id1 were found to have sustained inactivating p16/ink4a mutations. These data suggest a role for Id1 in regulating p16/Ink4a expression in early melanomas and demonstrate that later genetic changes may provide for irreversible loss of p16 expression in advanced stages of this tumor.
UI - 98241894
AU - Carli P; Biggeri A; Nardini P; De Giorgi V; Giannotti B
TI - Sun exposure and large numbers of common and atypical melanocytic naevi: an analytical study in a southern European population.
SO - Br J Dermatol 1998 Mar;138(3):422-5
AD - Department of Statistics, University of Florence, Italy.
The study analysed the relationship between high counts of common naevi and numbers of atypical naevi (AN) in sites differing in exposure to the sun. A series of 90 subjects with 100 or more common naevi (cases) and 92 controls was investigated by means of a case-control study. A striking association between high numbers of common naevi and prevalence of AN (whole body) was found. The adjustment for phenotype and phototype did not obscure this association. Similar findings were obtained after exclusion of subjects with familiarity for melanoma. Cases had more AN than controls in all the body sites, except for the buttocks, where sun exposure can be considered minimal or absent: in this site, an excess of common naevi but not of AN was found. The present study suggests that subjects with high common naevi counts show a higher prevalence of AN independently of their complexion, sunburn history and family history of melanoma. Phenotypic expression of AN seems to be enhanced by direct sun exposure.
UI - 21302033
AU - Yang FC; Merlino G; Chin L
TI - Genetic dissection of melanoma pathways in the mouse.
SO - Semin Cancer Biol 2001 Jun;11(3):261-8
AD - Department of Adult Oncology, Dana-Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Mayer 448, Boston, MA 02115, USA.
The frequent loss of the INK4a/ARF locus, encoding for both p16(INK4a)and p19(ARF)in human melanoma, raises the question as to which INK4a/ARF gene product functions to suppress melanoma-genesis in vivo. Studies in the mouse have shown that activated RAS mutation can cooperate with INK4a(Delta 2/3)deficiency (null for both p16(INK4a)and p19(ARF)) to promote development of melanoma, and these melanomas retain wild-type p53. Given the functional link between p19(ARF)and p53, we have now shown that activated RAS can also cooperate with p53 deficiency to produce melanoma in the mouse. Moreover, genome-wide analysis of RAS-induced p53 mutant melanomas reveals alterations of key components governing RB-regulated G1/S transition, such as c-Myc. These experimental findings suggest that both RB and p53 pathways function to suppress melanocyte transformation in vivo in the mouse. Copyright 2001 Academic Press.
UI - 21369962
AU - Muir AI; Chamberlain L; Elshourbagy NA; Michalovich D; Moore DJ; Calamari A; Szekeres PG; Sarau HM; Chambers JK; Murdock P; Steplewski K; Shabon U; Miller JE; Middleton SE; Darker JG; Larminie CG; Wilson S; Bergsma DJ; Emson P; Faull R; Philpott KL; Harrison DC
TI - AXOR12, a novel human G protein-coupled receptor, activated by the peptide KiSS-1.
SO - J Biol Chem 2001 Aug 3;276(31):28969-75
AD - Department of Discovery Biology, GlaxoSmithKline, New Frontiers Science Park, Harlow, Essex CM19 5AW, United Kingdom.
A novel human G protein-coupled receptor named AXOR12, exhibiting 81% homology to the rat orphan receptor GPR54, was cloned from a human brain cDNA library. Heterologous expression of AXOR12 in mammalian cells permitted the identification of three surrogate agonist peptides, all with a common C-terminal amidated motif. High potency agonism, indicative of a cognate ligand, was evident from peptides derived from the gene KiSS-1, the expression of which prevents metastasis in melanoma cells. Quantitative reverse transcriptase-polymerase chain reaction was used to study the expression of AXOR12 and KiSS-1 in a variety of tissues. The highest levels of expression of AXOR12 mRNA were observed in brain, pituitary gland, and placenta. The highest levels of KiSS-1 gene expression were observed in placenta and brain. A polyclonal antibody raised to the C terminus of AXOR12 was generated and used to show localization of the receptor to neurons in the cerebellum, cerebral cortex, and brainstem. The biological significance of these expression patterns and the nature of the putative cognate ligand for AXOR12 are discussed.
UI - 21413529
AU - Seftor RE; Seftor EA; Koshikawa N; Meltzer PS; Gardner LM; Bilban M; Stetler-Stevenson WG; Quaranta V; Hendrix MJ
TI - Cooperative interactions of laminin 5 gamma2 chain, matrix metalloproteinase-2, and membrane type-1-matrix/metalloproteinase are required for mimicry of embryonic vasculogenesis by aggressive melanoma.
SO - Cancer Res 2001 Sep 1;61(17):6322-7
AD - Department of Anatomy and Cell Biology, University of Iowa, Iowa City, Iowa 52242, USA.
Vasculogenic mimicry describes a process where aggressive tumor cells in three-dimensional matrices mimic embryonic vasculogenesis by forming extracellular matrix (ECM)-rich, patterned tubular networks. Microarray gene chip analyses revealed significant increases in the expression of laminin 5 (Ln-5, gamma2 chain) and matrix metalloproteinases (MMP)-1, -2, -9, and MT1-MMP (MMP-14) in aggressive compared with poorly aggressive melanoma cells. These components colocalized with developing patterned networks and antisense oligonucleotides to the Ln-5 gamma2 chain (but not sense oligonucleotides), and antibodies to MMP-2 or MT1-MMP (but not MMP-9) inhibited the formation of these networks. Cultures which did not receive antibodies to either MMPs-2 or -14 contained the Ln-5 gamma2 chain promigratory cleavage fragments. Poorly aggressive melanoma cells seeded on collagen I matrices preconditioned by the aggressive cells formed tubular networks along the Ln-5 gamma2 chain-enriched tracks deposited by the aggressive cells. These results suggest that increased expression of MMP-2 and MT1-MMP, along with matrix deposition of the Ln-5 gamma2 chain and/or its cleavage fragments, are required for vasculogenic mimicry by aggressive melanoma cells. Furthermore, the apparent recapitulation of laminin-rich, patterned networks observed in aggressive melanoma patients' tissue sections by aggressive melanoma tumor cells in three-dimensional culture may also serve as a model to help identify specific molecular targets which could function as templates for the coordinated migration of aggressive tumor cells and their proteolytic remodeling of the ECM and may have profound implications for the development of novel therapies directed at the ECM to alter tumor progression.
UI - 21311859
AU - Deffrennes V; Vedrenne J; Stolzenberg MC; Piskurich J; Barbieri G; Ting JP; Charron D; Alcaide-Loridan C
TI - Constitutive expression of MHC class II genes in melanoma cell lines results from the transcription of class II transactivator abnormally initiated from its B cell-specific promoter.
SO - J Immunol 2001 Jul 1;167(1):98-106
AD - Unite Institut National de la Sante et de la Recherche Medicale, Unite 396, Centre de Recherches Biomedicales des Cordeliers, Paris, France.
In melanoma cell lines, two different patterns of MHC class II expression have been described, either an IFN gamma-inducible expression of HLA-DR and HLA-DP, with a faint or null expression of HLA-DQ, resembling that described for melanocytes, or a constitutive expression, i.e., IFN-gamma independent, of all three HLA-D isotypes. As this latter phenotype has been associated with a more rapid progression of melanoma tumors, we have analyzed in different melanoma cell lines the molecular mechanisms leading to this abnormal pattern of MHC class II expression. In agreement with the evidence of a coordinate transcription of the HLA-D genes in these cell lines, we have shown the constitutive expression of CIITA (class II transactivator) transcripts, CIITA being known as the master switch of MHC class II expression. Unexpectedly, these transcripts initiate from promoter III of the CIITA gene, a promoter that is mainly used constitutively in B lymphocytes. This expression was further shown to occur through factor(s) acting on the enhancer located upstream of CIITA promoter III, which was previously described in epithelioid cells as an IFN-gamma-response sequence. The hypothesis of a general abnormality of the IFN-gamma transduction pathway was dismissed. Constitutive transcription of CIITA from promoter III having been observed in unrelated melanoma cell lines, we propose the hypothesis that this phenomenon might not be a random event, but could be linked to the neoplasic state of the melanoma cells.
UI - 21403081
AU - Kennedy C; ter Huurne J; Berkhout M; Gruis N; Bastiaens M; Bergman W; Willemze R; Bavinck JN
TI - Melanocortin 1 receptor (MC1R) gene variants are associated with an increased risk for cutaneous melanoma which is largely independent of skin type and hair color.
SO - J Invest Dermatol 2001 Aug;117(2):294-300
AD - Department of Dermatology, Leiden University Medical Center, RC Leiden, the Netherlands.
Individuals carrying melanocortin 1 receptor gene variants have an increased risk for the development of cutaneous melanoma. Melanocortin 1 receptor gene variants are also associated with other risk factors for melanoma such as fair skin and red hair. We evaluated the relationship of melanocortin 1 receptor gene variants, fair skin, red hair and the development of melanoma in 123 patients with cutaneous melanoma and 385 control subjects. To analyze the association between melanocortin 1 receptor gene variants and skin type or hair color we also made use of 453 patients with nonmelanoma skin cancer. We analyzed the coding sequence of the melanocortin 1 receptor gene region by single-stranded conformation polymorphism analysis, followed by DNA sequence analysis. Risk of melanoma dependent on the various melanocortin 1 receptor variant alleles was estimated by exposure odds ratios. The analyses of all different melanocortin 1 receptor gene variants combined, showed that the presence of melanocortin 1 receptor gene variants amounted to a higher melanoma risk, which, in stratified analyses, was independent of skin type and hair color. The odds ratios after adjusting for skin type were 3.6 (95% CI 1.7-7.2) for two variants and 2.7 (95% CI 1.5-5.1) for one variant, respectively. Compound heterozygotes and homozygotes for the Val60Leu, Val92Met, Arg142His, Arg151Cys, Arg160Trp, Arg163Gln, and His260Pro variants had odds ratios of about 4 to develop melanoma, whereas heterozygotes for these variants had half the risk. The presence of the melanocortin 1 receptor gene variant Asp84Glu appeared to impose the highest risk for cutaneous melanoma with odds ratios of 16.1 (95% CI 2.3-139.0) and 8.1 (95% CI 1.2-55.9) in compound heterozygotes and heterozygotes, respectively. The broad confidence intervals, when the different variants were analyzed separately, however, do not allow drawing definite conclusions about the magnitude of these risks. Of the more frequently occurring melanocortin 1 receptor variant alleles the Asp84Glu, Arg142His, Arg151Cys, Arg160Trp, His260Pro, and Asp294His variants were strongly associated with both fair skin and red hair. The Val60Leu, Val92Met, and Arg163Gln variant alleles, however, were only weakly or not associated with fair skin type and/or red hair, which further illustrates the finding that skin type, hair color, and melanoma are independent outcomes of the presence of melanocortin 1 receptor gene variants. We conclude that numerous melanocortin 1 receptor variants predispose to cutaneous melanoma and that possibly the Asp84Glu variant confers the highest risk. This predisposition is largely independent of skin type and hair color.
UI - 21409925
AU - Fujita H; Okada F; Hamada J; Hosokawa M; Moriuchi T; Koya RC; Kuzumaki N
TI - Gelsolin functions as a metastasis suppressor in B16-BL6 mouse melanoma cells and requirement of the carboxyl-terminus for its effect.
SO - Int J Cancer 2001 Sep15;93(6):773-80
AD - Division of Cancer Gene Regulation, Research Section of Disease Control, Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan. firstname.lastname@example.org
Gelsolin, an actin-binding protein, is implicated as a critical regulator in cell motility. In addition, we have reported that cellular levels of gelsolin are decreased in various tumor cells, and overexpression of gelsolin by gene transfer suppresses tumorigenicity. We sought to assess the effects of gelsolin overexpression on metastasis and to determine the importance of a carboxyl-terminus that confers Ca(2+) dependency on gelsolin for effects of its overexpression. Expression vectors with cDNA encoding either full-length wild-type or His321 mutant form, isolated from a flat revertant of Ras-transformed cells and a carboxyl-terminal truncate, C-del of gelsolin, were transfected into a highly metastatic murine melanoma cell line, B16-BL6. Expression of introduced cDNA in transfectants was confirmed using Western blotting, 2-dimensional gel electrophoresis and reverse transcription-polymerase chain reaction (RT-PCR). We characterized phenotypes of transfectants, such as growth rate, colony formation in soft agar, cell motility and metastasis formation in vivo. Transfectants expressing the wild-type, His321 mutant and C-del gelsolin exhibited reduced growth ability in soft agar. Although expression of integrin beta1 or alpha4 on the cell surface of transfectants was not changed, wild-type and His321 mutant gelsolin, except for C-del gelsolin, exhibited retardation of cell spreading, reduced chemotatic migration to fibronectin and suppressed lung colonization in spontaneous metastasis assay. Gelsolin may function as a metastasis suppressor as well as a tumor suppressor gene. The carboxyl-terminus of gelsolin is important for retardation of cell spreading, reduced chemotasis and metastasis suppression. Copyright 2001 Wiley-Liss, Inc.
UI - 21412206
AU - Chande M
TI - A marker for melanoma?
SO - Lancet 2001 Aug 18;358(9281):565
UI - 21397884
AU - Goldstein AM; Liu L; Shennan MG; Hogg D; Tucker MA; Struewing JP
TI - A common founder for the V126D CDKN2A mutation in seven North American melanoma-prone families.
SO - Br J Cancer 2001 Aug 17;85(4):527-30
AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA.
One of the most common melanoma-related CDKN2A mutations reported in North America is the V126D mutation. We examined nine markers surrounding CDKN2A in three American and four Canadian families carrying the V126D mutation. All seven families had a haplotype consistent with a common ancestor/founder for this mutation. In addition, the mutation appears to have originated 34-52 generations ago (1-LOD-unit support interval 13-98 generations). Copyright 2001 Cancer Research Campaign.
UI - 21230646
AU - Gunther K; Fleischer A; Buettner R; Bosserhoff AK
TI - Detection of invasion-related chromosomal changes in highly and weakly invasive melanoma cell clones by a modified comparative genomic hybridization approach.
SO - Melanoma Res 2001 Apr;11(2):105-15
AD - University Hospital RWTH Aachen, Institute of Pathology, Germany.
Invasion is a key step in the systemic spread of tumour cells. The aim of this study was to investigate whether specific chromosomal aberrations in melanoma occur during acquisition of a strongly invasive phenotype. We previously selected highly and weakly invasive cell clones from the human melanoma cell line Mel Im. Both cell clones retained a stable phenotype over more than 40 passages, revealing a five-fold difference in their invasive potential in vitro. Direct comparative genomic hybridization (CGH) (modified CGH) of the two cell clones was used as a powerful tool to screen for different chromosomal aberrations in both clones. Standard CGH and fluorescence in situ hybridization (FISH) was performed to verify the results of this improved technique. In general, the CGH pattern showed a high degree of identity consistent with the fact that the cell lines represent subclones of the same cell line. However, a few defined changes between the two cell clones were observed, including loss of 1q21-qter, 4q, 11p14-pter, 19q and 20p in the highly invasive cell clone. Two of the regions (1q and 11p) have already been suggested to be involved in melanoma progression, whereas changes in the others have not been detected before. In summary, our direct CGH approach proved to be suitable for fast and direct comparison of two cell types and allowed the identification of two known and three novel chromosomal changes involved in the acquisition of a strongly invasive melanoma cell phenotype.
UI - 21230647
AU - Avril MF; Chompret A; Verne-Fourment L; Terrier-Lacombe MJ; Spatz A; Fizazi K; Bressac-de Paillerets B; Demenais F; Theodore C
TI - Association between germ cell tumours, large numbers of naevi, atypical naevi and melanoma.
SO - Melanoma Res 2001 Apr;11(2):117-22
AD - Department of Dermatology, Institut Gustave Roussy, Villejuif, France.
Identifying groups of subjects at high risk for the development of melanoma is crucial for the early diagnosis of curable tumours. In the present study, we performed a skin examination in a group of 63 patients followed up after treatment of germ cell tumours (GCTs) who were referred to the dermatologist for multiple pigmented cutaneous spots. Forty-nine patients bearing a great number of naevi or atypical naevi were included in the study. Two thin cutaneous melanomas were discovered in two patients. In addition, a third patient had had a conjunctival melanoma since treatment of the GCT. Our study confirms the presence of atypical naevi in a subgroup of GCT patients, who are shown to be at high risk of developing melanoma. Patients harbouring multiple pigmented spots should be referred for a skin examination aimed at early detection of curable melanomas, and should be advised to protect themselves from sun exposure.
UI - 21230649
AU - Hemminki K; Lonnstedt I; Vaittinen P
TI - A population-based study of familial cutaneous melanoma.
SO - Melanoma Res 2001 Apr;11(2):133-40
AD - Department of Biosciences at Novum, Karolinska Institute, Huddinge, Sweden. Kari.Hemminki@cnt.ki.se
We studied familial risks in cutaneous melanoma by comparing the occurrence of melanoma, or discordant cancer, in two generations, based on the Swedish Family-Cancer Database of 9.6 million individuals. Offspring were from 0 to 61 years of age. Cancers were obtained from the Swedish Cancer Registry for the years 1958 to 1996. The study was based on 30,170 cases of melanoma. Among these, 196 offspring came from families where a parent also presented with melanoma. The overall familial hazard ratio (FHR) was 2.47 when a parent had melanoma; an early age of onset increased the risk. Multiple primary melanomas in parents increased the FHR in offspring, being 2.23 for one, 9.10 for two and up to 83 for more than two melanomas in the parent. The number of affected offspring increased the risk of melanoma in the parents, from 3.05 when one was affected to 5.12 and 151 when two or three offspring were affected, respectively. Melanoma risk to a sibling with an affected proband was 3.56. Melanoma in one generation was associated with an increased occurrence of squamous cell carcinoma of the skin in the other generation. Other weaker associations were found to pancreatic, breast, testicular and nervous system cancers and non-Hodgkin lymphomas.
UI - 21331829
AU - Hussein MR; Sun M; Tuthill RJ; Roggero E; Monti JA; Sudilovsky EC; Wood GS; Sudilovsky O
TI - Comprehensive analysis of 112 melanocytic skin lesions demonstrates microsatellite instability in melanomas and dysplastic nevi, but not in benign nevi.
SO - J Cutan Pathol 2001 Aug;28(7):343-50
AD - Institute of Pathology, Case Western Reserve University and University Hospitals of Cleveland, Cleveland, Ohio, USA.
INTRODUCTION: the length of DNA repetitive sequences (microsatellite instability (MSI)) represent distinct tumorigenic pathways associated with several familial and sporadic tumors. MATERIAL AND METHODS: To investigate the prevalence and frequency of MSI in melanocytic lesions, the polymerase chain reaction (PCR)-based microsatellite assay was used to examine formalin-fixed, paraffin-embedded tissues of 30 benign melanocytic nevi, 60 melanocytic dysplastic nevi (MDN), and 22 primary vertical growth phase cutaneous malignant melanomas (CMM). Twenty-four microsatellite markers at the 1p, 2p, 3p, 4q and 9p chromosomal regions were used. RESULTS: MSI was found at 1p and 9p in MDN and CMM but not in benign melanocytic nevi. The overall prevalence of MSI was 17/60 (28%) in MDN and 7/22 (31%) in CMM. The frequency of MSI ranged from 2/24 (9%) to 4/24 (17%) and was most commonly found at D9S162. There was a statistically significant correlation between degree of atypia and frequency of MSI (p<0.001) in MDN. There were two MSI banding patterns: band shifts and additional bands. CONCLUSIONS: The data presented revealed the presence of low-frequency MSI (MSI-L) at the 1p and 9p regions in both MDN and CMM. Whether the MSI-L pattern reflects a defect in mismatch repair genes is still to be determined.
UI - 21349559
AU - Padilla Parrado M; Saez Castillo AI; Galan Morales JT; Orradre Romeo JL; Delgado Quero AL; Sanchez Carrion S
TI - [Malignant melanoma of the nasal cavity. Retrospective study. The analysis of p53 and p16INK4 expression]
SO - An Otorrinolaringol Ibero Am 2001;28(3):303-16
AD - Hospital Virgen de La Salud, Toledo.
Five cases of malignant melanomata of the nasal cavities have been diagnosed and studied at ENT--and Anatomopathological Departments, between 1990 and 1997, the group ranging from 65 to 90 years, middle age 74.2. Paramount symptoms were epistaxis and lack of pain in all patients. Radical surgery was performed only in one case, followed by radiotherapy; the remainder were submitted to palliative treatment. We have reviewed the literature and also an immunohistochemical analysis about p53, p16INK4 and Rb oncogenes with the aim to establish its importance in these tumor's type. The whole group have showed high levels of p53 and MIB-1 and 60 percent a loss of oncogen p16 expression.
UI - 21361587
AU - Wang Z; Atencio J; Robinson ES; McCarrey JR
TI - Ultraviolet B-induced melanoma in Monodelphis domestica occurs in the absence of alterations in the structure or expression of the p53 gene.
SO - Melanoma Res 2001 Jun;11(3):239-45
AD - Department of Genetics, Southwest Foundation for Biomedical Research, PO Box 760549, San Antonio, TX 78227-5301, USA.
Monodelphis domestica, a South American opossum, has been established as a mammalian model for sporadic ultraviolet radiation (UVR)-induced melanoma. Using this model system, we investigated the role of changes in the p53 gene in the development of cutaneous melanocyte-derived lesions. Cutaneous melanocytic hyperplasias, benign melanomas and metastatic primary melanomas, plus affected lymph nodes and visceral organs, were screened for mutations in the Monodelphis p53 gene by single-strand conformation polymorphism analysis and direct sequencing. With the exception of a silent point mutation found in a single benign melanocytic hyperplasia sample, no p53 mutations were detected. Furthermore, a relative quantitative reverse transcriptase-polymerase chain reaction approach was used to analyse p53 gene expression at different stages of primary melanoma progression and revealed no substantial changes in p53 mRNA levels. These results suggest that, as in humans, UVR-induced melanoma in the Monodelphis model is initiated and progresses on the basis of predominantly p53-independent molecular pathways.
UI - 21361589
AU - Singh AD; Shields CL; Shields JA
TI - Prognostic factors in uveal melanoma.
SO - Melanoma Res 2001 Jun;11(3):255-63
AD - Oncology Service, Wills Eye Hospital, Thomas Jefferson University, 900 Walnut Street, Philadelphia, PA 19107, USA.
Uveal melanoma is the most common primary intraocular malignant tumour, with an annual incidence of approximately six cases per million per year. Approximately 40% of patients with posterior uveal melanoma develop metastatic melanoma to the liver within 10 years after initial diagnosis. Despite high accuracy of diagnosis and availability of various methods of treatment; the mortality due to uveal melanoma has remained unchanged. The prognosis in uveal melanoma depends on clinical, histopathological and cytological factors. Clinical factors that relate to prognosis include location, size, and configuration of the tumour. Uveal melanoma can arise in the iris, the ciliary body or the choroid. Iris melanomas have the best prognosis and ciliary body melanomas have the worst prognosis. Based on retrospective studies, the mortality rates for uveal melanoma for comparable sized tumours treated by enucleation or other globe conserving methods such as radiotherapy appear to be similar. Histopathological factors such as cell type, mitotic activity, microcirculation architecture, tumour-infiltrating lymphocytes and the presence of extrascleral extension are also significant predictors of survival. More recently, cytological factors such as cell proliferation, cytogenic, and molecular genetic prognostic markers have been identified with the hope of detecting high risk cases for adjuvant systemic immune therapy or chemotherapy. At present, the role of these therapeutic methods is not clearly established.
UI - 21361592
AU - Richetta A; Ottini L; Falchetti M; Innocenzi D; Bottoni U; Faiola R; Mariani-Costantini R; Calvieri S
TI - Instability at sequence repeats in melanocytic tumours.
SO - Melanoma Res 2001 Jun;11(3):283-9
AD - Institute of Dermatology, Policlinico Umberto I, University La Sapienza, Rome, Italy.
To obtain information on the prevalence of microsatellite mutations in melanomas, we analysed the status of 14 repetitive loci characterized by structurally different non-coding and coding sequence repeats in a panel of 34 primary melanocytic tumours and in lymph node metastases matched to 13 cases. Instability at one or more of the non-coding dinucleotide repeats D2S123, D3S1611, D5S107 and D18S34 was detected in ten out of the 34 primary tumours (29%) and in ten of the 13 metastases (77%). There was no instability at the non-coding mononucleotide repeats BAT25, BAT26 and APDelta3 or at the coding mononucleotide runs within the TGFbetaRII, IGFIIR, BAX, hMSH3 and hMSH6 genes. A five-repeats expansion of the coding E2F4(CAG)n run was found in the only malignant melanoma of soft parts examined, which also showed instability at two dinucleotide loci, and in a superficial spreading melanoma, which was stable at the mononucleotide and dinucleotide repeats but was the only tumour that manifested instability at the SCA1(CAG)n repeat. The absence of mutations at mononucleotide tracts indicates that, in the malignant melanomas tested, microsatellite instability was not associated with the microsatellite mutator phenotype characteristic of mismatch repair-deficient tumours. On the other hand, our results confirm that microsatellite instability at dinucleotide repeats increases with melanoma progression, and indicate that expansions of triplet repeats may occur in melanocytic tumours.
UI - 21363225
AU - Samija M; Juretic A; Solaric M; Samija I; Bingulac-Popovic J; Grahovac B; Stanec M; Oresic V
TI - RT-PCR detection of tyrosinase, gp100, MART1/Melan-A, and TRP-2 gene transcripts in peripheral blood of melanoma patients.
SO - Croat Med J 2001 Aug;42(4):478-83
AD - University Hospital for Tumors, Zagreb, Croatia.
AIM: To detect the expression of genes encoding tyrosinase, gp100, MART-1/Melan A, and tyrosinase-related protein-2 (TRP-2) in peripheral blood of melanoma patients by reverse transcription-polymerase chain reaction (RT-PCR). METHODS: Nineteen peripheral blood samples were obtained from 17 melanoma patients. When tested, 15 of them presented with clinically detectable metastatic disease. Samples of peripheral blood (7 mL) were collected from each patient into vacutainer cell preparation tubes. Mononuclear cells were isolated, total cellular RNA extracted, and then used as a template for reverse transcription to complementary DNA (cDNA). The cDNA was thereafter assayed by PCR for the expression of melanocyte-associated transcripts of tyrosinase, gp100, MART1/Melan-A, and TRP-2 genes. RESULTS: Gp100 gene expression was detected in 13 out of 19 samples. In 4 of them, TRP-2 gene expression was also detectable. Expression of tyrosinase and Melan-A/MART-1 genes could not be observed. Interestingly, gp100 and TRP-2 gene transcripts were detected in patients having recurrent and/or metastatic disease at the time of testing. CONCLUSION: The results we obtained support the use of RT-PCR assay for indirect detection of melanoma cells in peripheral blood of melanoma patients. As the transcripts for the tyrosinase gene and MART-1/Melan A gene were not detected, additional optimization experiments of RT-PCR assay are required.
UI - 21417225
AU - Augusseau-Caillot A; Soler C; Teyssier F; Perrot JL; Tiffet O; Cambazard F; Cuilleret J; Dumollard JM
TI - Interest of PS100 assay when (99m)Tc sestamibi scintigraphy failed to identify lymph node metastases of melanoma.
SO - Eur J Dermatol 2001 Sep-Oct;11(5):432-5
AD - Laboratoire de Biologie du Tissus Osseux, Faculte de Medecine J.-Lisfranc, 42100 Saint-Etienne, France.
The study evaluated the contribution of serum PS100 assay to the detection of lymph node metastases during the follow-up of patients previously treated for a malignant melanoma, in addition to (99m)Tc sestamibi (MIBI) scintigraphy and investigation for gene MDR1, in order to detect chemoresistance phenomena. The study included 37 patients with a clinically questionable lymph node around basin lymphatic areas of the previously surgically-treated malignant melanoma. The sensitivity and specificity of PS100 assay were 91% and 86.5%, respectively. The sensitivity and specificity of MIBI scintigraphy were 95% and 85%, respectively. Overexpression of gene MDR1 was observed in six cases. In the event of negative scintigraphic findings, the concomitant analysis of PS100 levels and the scintigraphic result enabled the metastatic MDR+ patients to be distinguished from the non-metastatic patients. PS100 assay may therefore be proposed for the follow-up of malignant melanoma.