Germline mutations of the INK4a-ARF gene in patients with suspected genetic predisposition to melanoma

被引:31
作者
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
机构
[1] Hop Bichat Claude Bernard, Lab Biochim Hormonale & Genet, F-75018 Paris, France
[2] Fac Bichat Claude Bernard, INSERM, U410, F-75018 Paris, France
[3] Hop Robert Debre, Biochim Genet Lab, F-75018 Paris, France
[4] Hop Bichat Claude Bernard, Dept Dermatol, F-75018 Paris, France
[5] Hop St Louis, Dept Dermatol, F-75010 Paris, France
[6] Hop Percy, Dept Dermatol, F-92140 Clamart, France
[7] Hop Ambroise Pare, Dept Dermatol, Billancourt, France
关键词
INK4a-ARF; Cdk4; melanoma genetics; germline mutation; deletion;
D O I
10.1038/sj.bjc.6601503
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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 (2 1 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.
引用
收藏
页码:503 / 509
页数:7
相关论文
共 68 条
[1]   CDKN2A variants in a population-based sample of queensland families with melanoma [J].
Aitken, J ;
Welch, J ;
Duffy, D ;
Milligan, A ;
Green, A ;
Martin, N ;
Hayward, N .
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, 1999, 91 (05) :446-452
[2]   The CDKN2A tumour suppressor gene:: no mutations detected in patients with melanoma and additional unrelated cancers [J].
Alao, JP ;
Mohammed, MQ ;
Retsas, S .
MELANOMA RESEARCH, 2002, 12 (06) :559-563
[3]   Regulation of p53 stability [J].
Ashcroft, M ;
Vousden, KH .
ONCOGENE, 1999, 18 (53) :7637-7643
[4]   Sporadic multiple primary melanoma cases:: CDKN2A germline mutations with a founder effect [J].
Auroy, S ;
Avril, MF ;
Chompret, A ;
Pham, D ;
Goldstein, AM ;
Bianchi-Scarrá, G ;
Frebourg, T ;
Joly, P ;
Spatz, A ;
Rubino, C ;
Demenais, F ;
Bressac-de Paillerets, B .
GENES CHROMOSOMES & CANCER, 2001, 32 (03) :195-202
[5]  
Bahuau M, 1998, CANCER RES, V58, P2298
[6]   The melanocortin-1-receptor gene is the major freckle gene [J].
Bastiaens, M ;
ter Huurne, J ;
Gruis, N ;
Bergman, W ;
Westendorp, R ;
Vermeer, BJ ;
Bavinck, JNB .
HUMAN MOLECULAR GENETICS, 2001, 10 (16) :1701-1708
[7]  
Becker TM, 2001, CLIN CANCER RES, V7, P3282
[8]   CDKN2A, CDKN2B, and MTAP gene dosage permits precise characterization of mono- and bi-allelic 9p21 deletions in childhood acute lymphoblastic leukemia [J].
Bertin, R ;
Acquaviva, C ;
Mirebeau, D ;
Guidal-Giroux, C ;
Vilmer, E ;
Cavé, H .
GENES CHROMOSOMES & CANCER, 2003, 37 (01) :44-57
[9]   An assessment of the CDKN2A variant Ala148Thr as a nevus/melanoma susceptibility allele [J].
Bertram, CG ;
Gaut, RM ;
Barrett, JH ;
Pinney, E ;
Whitaker, L ;
Turner, F ;
Bataille, V ;
Silvaj, ID ;
Swerdlow, AJ ;
Bishop, DT ;
Bishop, JAN .
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2002, 119 (04) :961-965
[10]   High frequency of multiple melanomas and breast and pancreas carcinomas in CDKN2A mutation-positive melanoma families [J].
Borg, Å ;
Sandberg, T ;
Nilsson, K ;
Johannsson, O ;
Klinker, M ;
Måsbäck, A ;
Westerdahl, J ;
Olsson, H ;
Ingvar, C .
JOURNAL OF THE NATIONAL CANCER INSTITUTE, 2000, 92 (15) :1260-1266