Features associated with germline CDKN2A mutations: a GenoMEL study of melanoma-prone families from three continents

Goldstein, Alisa M.; Chan, May P.; Harland, Mark; Hayward, Nicholas K.; Demenais, Florence; Bishop, D. Timothy; Azizi, Esther; Bergman, Wilma; Bianchi‐Scarrǎ, Giovanna; Bruno, William; Calista, Donato; Cannon‐Albright, Lisa A.; Chaudru, Valérie; Chompret, Agnès; Cuéllar, Francisco; Elder, David E.; Ghiorzo, Paola; Gillanders, Elizabeth M.; Gruis, Nelleke A.; Hansson, Johan; Hogg, David; Holland, Elizabeth A.; Kanetsky, Peter A.; Kefford, Richard; Landi, Maria Teresa; Lang, Julie; Leachman, Sancy A.; MacKie, Rona M.; Magnusson, Veronica; Mann, Graham J.; Newton-Bishop, Julia; Palmer, Jane M.; Puig, Susana; Puig-Butillé, Joan Antón; Stark, Mitchell; Tsao, Hensin; Tucker, Margaret A.; Whitaker, Linda; Yakobson, Emanuel

doi:10.1136/jmg.2006.043802

Cited by 376 publications

(369 citation statements)

References 43 publications

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“…Only about 2 % of all melanoma cases in the population carry a CDKN2A mutation, but the probability is much higher when a strong family history of melanoma or multiple primary tumors are present [26,87]; as such, CDKN2A mutations are estimated to account for approximately 40 % of familial cases [87]. Carriers of a CDKN2A mutation have a substantial lifetime risk of developing cutaneous malignant melanoma; population-based estimates indicate that around 30-50 % of mutation carriers will develop melanoma by 80 years of age [20,58], whereas lifetime risk estimates derived from clinic-based sampling (of families with multiple cases of melanoma) range from 58 to 90 % penetrance by 80 years of age [27].…”

Section: Germline Genetic Factors and Genome-wide Associationmentioning

confidence: 99%

Melanoma Epidemiology and Prevention

Berwick

Buller

Cust

et al. 2015

Cancer Treatment and Research

122

121

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The epidemiology of melanoma is complex, and individual risk depends on sun exposure, host factors, and genetic factors, and in their interactions as well. Sun exposure can be classified as intermittent, chronic, or cumulative (overall) exposure, and each appears to have a different effect on type of melanoma. Other environmental factors, such as chemical exposures-either through occupation, atmosphere, or food-may increase risk for melanoma, and this area warrants further study. Host factors that are well known to be important are the numbers and types of nevi and the skin phenotype. Genetic factors are classified as

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Section: Germline Genetic Factors and Genome-wide Associationmentioning

confidence: 99%

Melanoma Epidemiology and Prevention

Berwick

Buller

Cust

et al. 2015

Cancer Treatment and Research

122

121

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“…Each of them corresponds to a pair of oligonucleotides that hybridize next each other on a specific chromosome site [68][69][70][71][72]. In addition to target-specific sites, both oligonucleotides contain a universal PCR primer.…”

Section: Mlpa Methodsmentioning

confidence: 99%

“…However, searching for such p16 mutations is clinically inrelevant in other CMM patients due to the weak probability of detecting the mutation [78]. A number of different p16 mutations have been reported so far [79]. The prevalence of familial p16 mutations is linked to the number of CMM in relatives.…”

Section: Germline and Somatic Cmm Mutationsmentioning

confidence: 99%

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Streamlining Molecular Pathobiology of Malignant Melanoma

Pierard¹

2016

CRDOA

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Currently, regular histopathology and immunohistochemistry are commonly taken for granted in the diagnosis of Cutaneous Malignant Melanoma (CMM). In addition, attempts at molecular diagnosis in dermatopathology have benefited from advances in pathobiology genomics and proteomics. They provide utmost information for optimal patient care. Sensitive techniques detect specific DNA and RNA sequences, and molecular methods were refined in the field of polypeptides. This review aims at covering on an overall glance about molecular genetics available as diagnostic supports in CMM. Laboratory methods have disclosed and highlighted some pathogenic pathways of atypical melanocytic neoplasms with particular emphasis on the activation of the Mitogen-Activated Protein Kinase (MAPK) signalling pathway (including BRAF and KIT) during the initiation step of the neoplasms. Many familial CMM contain mutations of the tumor suppressor gene p16 or CDKN2A. In addition, mutations in p53 are found in distinct CMM types. Many CMM are likely related to a variety of common low penetrance genes. Molecular dermatopathology represents a promising tool for both research and diagnosis. Knowledge of tumor mutation status is becoming increasingly important. The expected benefit of molecular dermatopathology tends to ultimately improve the targeted patient management. Such method evolution points to a need for improving the routine training requirements for dermatopathologists involved in cancer diagnostic responsibilities.

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“…35 In families studied in North America, Europe and Australia, the germline mutations responsible for the occurrence of melanoma and the phenotype of atypical nevus syndrome mainly affect exon 2, which is common to both transcripts of this gene, p16 and p14. 36 In a study by Leon et al (2008), conducted at AC Camargo Hospital in Sao Paulo, Brazil, with 40 families, a mutation detection rate of 25%, was observed, and these mutations were found in similar frequencies in different regions of the gene (unpublished data). Another gene, CDK4, may also be associated with familial melanoma syndrome and, consequently, with the occurrence of atypical nevi, but of much less importance, involving about 1% of affected families.…”

Section: Molecular Biologymentioning

confidence: 99%

Nevo displásico (nevo atípico)

Rezze

Duprat

2010

An. Bras. Dermatol.

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Atypical nevum (dysplastic) is considered an important factor associated with increased risk of developing cutaneous melanoma. It is believed that atypical nevi are precursor lesions of cutaneous melanoma. They may be present in patients with multiple melanocytic nevi (atypical nevus syndrome) or isolated and in small numbers in a non-familial context. The disease usually begins at puberty and predominates in young people. It has a predilection for sun-exposed areas, especially the trunk. The major challenge in relation to atypical nevi lies in the controversy of defining its nomenclature, clinical diagnosis, dermoscopic criteria, histopathological diagnosis and molecular aspects. This review aims at bringing knowledge, facilitating comprehension and clarifying doubts about atypical nevus. Keywords: Nevi and melanomas; dermoscopy; Histology Resumo: O nevo atípico (displásico) é considerado um fator importante associado com o risco aumentado de desenvolvimento do melanoma cutâneo. Acredita-se que nevos atípicos sejam lesões precursoras do melanoma cutâneo. Podem estar presentes em pacientes com múltiplos nevos melanocíticos (síndrome do nevo atípico) ou isolados e em poucas quantidades em um contexto não familial. Aparecem, geralmente, na puberdade e prevalecem em indivíduos jovens. Têm predileção por áreas expostas ao sol, especialmente, o tronco. O grande desafio em relação ao nevo atípico reside na controvérsia em se definir sua nomenclatura, diagnóstico clínico, critérios dermatoscópicos, diagnóstico histopatológico e aspectos moleculares. Esta revisão tem por objetivo trazer o conhecimento, facilitar o entendimento e responder às questões duvidosas concernentes ao nevo atípico.

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Features associated with germline CDKN2A mutations: a GenoMEL study of melanoma-prone families from three continents

Cited by 376 publications

References 43 publications

Melanoma Epidemiology and Prevention

Melanoma Epidemiology and Prevention

Streamlining Molecular Pathobiology of Malignant Melanoma

Nevo displásico (nevo atípico)

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