Melanoma: Bertrand G

Lesimple T, Voigt JJ, Bataillard A, Coindre JM, Culine S, Lortholary A, Merrouche Y, Ganem G, Kaminsky MC, Negrier S, Perol M, Bedossa P, Bertrand G, Bugat R, Fizazi K, Anonymous00330. · Oncologue médical, Centre Eugène Marquis, Rennes. · Bull Cancer. · Pubmed #14715428 links to  free full text

Abstract: CONTEXT: The "Standards, Options and Recommendations" (SOR) project, which started in 1993, is a collaboration between the Federation of French Cancer Centers (FNCLCC), the 20 French Regional Cancer Centers, and specialists from French public universities, general hospitals and private clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and the outcome of cancer patients. OBJECTIVES: To define Clinical Practice Guidelines (CPG) for the diagnosis of carcinomas of unknown primary site. METHODS: The methodology is based on a literature review and critical appraisal by a multidisciplinary group of experts who define the CPGs according to the definitions of the Standards, Options and Recommendations project. Once the guidelines has been defined, the document is submitted for review by independent reviewers. RESULTS: The main recommendations for the diagnosis of carcinomas of unknown primary site are: 1) Diagnostic strategy should aim to identify anatomoclinical entities of carcinomas of unknown primary site for which there is a specific treatment. For other anatomoclinical entities, identification of the primary tumour has no impact on the prognostic or therapeutic consequences, thus a systematic complete assessment is unnecessary. 2) An immunohistochemical investigation for the diagnosis should be performed using an appropriate panel of specific antibodies. This should enable the diagnosis of lymphoma, melanoma, germ cell tumour and sarcoma to be eliminated and the diagnosis of prostate, breast, ovary, thyroid or neuroendocrine tumours to be positively identified. 3) A sample can be frozen to enable typing, cytogenetic and, particularly, molecular biological studies to be performed later. 4) The clinician and pathologist should compare their opinions before and after the pathological diagnosis.

Soufir N, Meziani R, Lacapère JJ, Bertrand G, Fumeron F, Bourillon A, Gérard B, Descamps V, Crickx B, Ollivaud L, Archimbaud A, Lebbe C, Basset-Seguin N, Saiag P, Grandchamp B, Anonymous00433. · Laboratoire de Biochimie Hormonale et Génétique, Hôpital Bichat-Claude Bernard, AP-HP, Faculté de Médecine, Paris VII, Paris, France. · J Natl Cancer Inst. · Pubmed #16145050 links to  free full text

Abstract: The endothelin signaling pathway plays a crucial role in melanocyte differentiation and migration. In this study, we investigated whether germline mutations of endothelin receptor B (EDNRB), a gene involved in Hirschsprung disease (HSCR), could also predispose for malignant melanoma (MM). The coding region of EDNRB was sequenced in 137 MM patients and in 130 ethnically matched Caucasian control subjects. Six nonsynonymous EDNRB variants were found in 15 patients (11%), but only two were found in four control subjects (3%, odds ratio [OR] = 3.87, 95% confidence interval [CI] = 1.25 to 12; P = .012). Overall, 14 out of 15 MM patients carried EDNRB mutations reported in HSCR, some of which had previously been shown to lead to loss of function. In multivariable logistic regression analysis including skin type, eye and hair color, number of nevi, and dorsal lentigines (freckles), the association between EDNRB mutations and MM risk remained statistically significant (OR = 19.9, 95% CI = 1.34 to 296.2; P = .03). Our data strongly suggest that EDNRB is involved in predisposition for two different multigenic disorders, HSCR and melanoma.

Jannot AS, Meziani R, Bertrand G, Gérard B, Descamps V, Archimbaud A, Picard C, Ollivaud L, Basset-Seguin N, Kerob D, Lanternier G, Lebbe C, Saiag P, Crickx B, Clerget-Darpoux F, Grandchamp B, Soufir N, Melan-Cohort. · Unite INSERM 535 'Génétique Epidémiologique et Structure des Populations Humaines', Hôpital Paul Brousse, Villejuif, France. · Eur J Hum Genet. · Pubmed #15889046 links to  free full text

Abstract: The occuloalbinism 2 (OCA2) gene, localized at 15q11, encodes a melanosomal transmembrane protein that is involved in the most common form of human occulo-cutaneous albinism, a human genetic disorder characterized by fair pigmentation and susceptibility to skin cancer. We wondered whether allele variations at this locus could influence susceptibility to malignant melanoma (MM). In all, 10 intragenic single-nucleotide polymorphisms (SNPs) were genotyped in 113 patients with melanomas and in 105 Caucasian control subjects with no personal or family history of skin cancer. By comparing allelic distribution between cases and controls, we show that MM and OCA2 are associated (p value=0.030 after correction for multiple testing). Then, a recently developed strategy, the 'combination test' enabled us to show that a combination formed by two SNPs was most strongly associated to MM, suggesting a possible interaction between intragenic SNPs. In addition, the role of OCA2 on MM risk was also detected using a logistic model taking into account the presence of variants of the melanocortin 1 receptor gene (MC1R, a key pigmentation gene) and all pigmentation characteristics as melanoma risk factors. Our data demonstrate that a second pigmentation gene, in addition to MC1R, is involved in genetic susceptibility to melanoma.

Matichard E, Verpillat P, Meziani R, Gérard B, Descamps V, Legroux E, Burnouf M, Bertrand G, Bouscarat F, Archimbaud A, Picard C, Ollivaud L, Basset-Seguin N, Kerob D, Lanternier G, Lebbe C, Crickx B, Grandchamp B, Soufir N. · No affiliation provided · J Med Genet. · Pubmed #14757863 links to  free full text

This publication has no abstract.

Soufir N, Lacapere JJ, Bertrand G, Matichard E, Meziani R, Mirebeau D, Descamps V, Gérard B, Archimbaud A, Ollivaud L, Bouscarat F, Baccard M, Lanternier G, Saïag P, Lebbé C, Basset-Seguin N, Crickx B, Cave H, Grandchamp B. · Laboratoire de Biochimie Hormonale et Génétique, Hôpital Bichat-Claude Bernard, 46 rue henri Huchard, Paris 75018, France. · Br J Cancer. · Pubmed #14735200 links to  free full text

Abstract: Germline anomalies of the INK4a-ARF and Cdk4 genes were sought in a series of 89 patients suspected of having a genetic predisposition to melanoma. Patients were selected based on the following criteria: (a) familial melanoma (23 cases), (b) multiple primary melanoma (MPM; 18 cases), (c) melanoma and additional unrelated cancers (13 cases), (d) age at diagnosis less than 25 years (21 cases), and (e) nonphoto-induced melanoma (NPIM; 14 cases). Mutations of INK4a-ARF and Cdk4 were characterised by automated sequencing, and germline deletions of INK4a-ARF were also examined by real-time quantitative PCR. Seven germline changes of INK4a-ARF, five of which were novel, were found in seven patients (8%). Four were very likely to be pathogenic mutations and were found in three high-risk melanoma families and in a patient who had a pancreatic carcinoma in addition to melanoma. Three variants of uncertain significance were detected in one MPM patient, one patient <25 years, and one NPIM patient. No germline deletion of INK4a-ARF was found in 71 patients, and no Cdk4 mutation was observed in the 89 patients. This study confirms that INK4a-ARF mutations are infrequent outside stringent familial criteria, and that germline INK4a-ARF deletions are rarely involved in genetic predisposition to melanoma.

Soufir N, Ollivaud L, Bertrand G, Lacapère JJ, Descamps V, Vitoux D, Lebbe C, Wolkenstein P, Dupin N, Saiag P, Basset-Seguin N, Grandchamp B, Anonymous00197. · No affiliation provided · J Dermatol Sci. · Pubmed #17223014 No free full text.

This publication has no abstract.

Meziani R, Descamps V, Gérard B, Matichard E, Bertrand G, Archimbaud A, Ollivaud L, Saiag P, Lebbé C, Basset-Seguin N, Alberti C, Crickx B, Grandchamp B, Soufir N. · No affiliation provided · J Dermatol Sci. · Pubmed #16183259 No free full text.

This publication has no abstract.