A Comparison of CDKN2A Mutation Detection Within the Melanoma Genetics Consortium (GenoMEL)

Overview

Journal Eur J Cancer

Specialty Oncology

Date 2008 Apr 9

PMID 18394881

Citations 16

Authors

Mark Harland

Alisa M Goldstein

Kairen Kukalizch

Claire Taylor

David Hogg

Susana Puig

Celia Badenas

Nelleke Gruis

Jeanet Ter Huurne

Wilma Bergman

Nicholas K Hayward

Mitchell Stark

Hensin Tsao

Margaret A Tucker

Maria Teresa Landi

Giovanna Bianchi Scarra

Paola Ghiorzo

Peter A Kanetsky

David Elder

Graham J Mann

Elizabeth A Holland

D Timothy Bishop

Julia Newton Bishop

Affiliations

Soon will be listed here.

Abstract

CDKN2A is the major melanoma susceptibility gene so far identified, but only 40% of three or more case families have identified mutations. A comparison of mutation detection rates was carried out by "blind" exchange of samples across GenoMEL, the Melanoma Genetics Consortium, to establish the false negative detection rates. Denaturing high performance liquid chromatography (DHPLC) screening results from 451 samples were compared to screening data from nine research groups in which the initial mutation screen had been done predominantly by sequencing. Three samples with mutations identified at the local centres were not detected by the DHPLC screen. No additional mutations were detected by DHPLC. Mutation detection across groups within GenoMEL is carried out to a consistently high standard. The relatively low rate of CDKN2A mutation detection is not due to failure to detect mutations and implies the existence of other high penetrance melanoma susceptibility genes.

Citing Articles

Novel Anaplastic Thyroid Cancer PDXs and Cell Lines: Expanding Preclinical Models of Genetic Diversity.

Maniakas A, Henderson Y, Hei H, Peng S, Chen Y, Jiang Y J Clin Endocrinol Metab. 2021; 106(11):e4652-e4665.

PMID: 34147031 PMC: 8530744. DOI: 10.1210/clinem/dgab453.

Estimating CDKN2A mutation carrier probability among global familial melanoma cases using GenoMELPREDICT.

Taylor N, Mitra N, Qian L, Avril M, Bishop D, Bressac-de Paillerets B J Am Acad Dermatol. 2019; 81(2):386-394.

PMID: 30731170 PMC: 6634996. DOI: 10.1016/j.jaad.2019.01.079.

Constitutional mutation in CDKN2A is associated with long term survivorship in multiple myeloma: a case report.

Shah V, Boyd K, Houlston R, Kaiser M BMC Cancer. 2017; 17(1):718.

PMID: 29110637 PMC: 5674776. DOI: 10.1186/s12885-017-3715-5.

Germline Variation at CDKN2A and Associations with Nevus Phenotypes among Members of Melanoma Families.

Taylor N, Mitra N, Goldstein A, Tucker M, Avril M, Azizi E J Invest Dermatol. 2017; 137(12):2606-2612.

PMID: 28830827 PMC: 5701856. DOI: 10.1016/j.jid.2017.07.829.

Phenotypic and Histopathological Tumor Characteristics According to CDKN2A Mutation Status among Affected Members of Melanoma Families.

Taylor N, Handorf E, Mitra N, Avril M, Azizi E, Bergman W J Invest Dermatol. 2016; 136(5):1066-1069.

PMID: 26827760 PMC: 5287416. DOI: 10.1016/j.jid.2016.01.009.

References

Parry D, Peters G . Temperature-sensitive mutants of p16CDKN2 associated with familial melanoma. Mol Cell Biol. 1996; 16(7):3844-52. PMC: 231381. DOI: 10.1128/MCB.16.7.3844. View

Frueh F, Noyer-Weidner M . The use of denaturing high-performance liquid chromatography (DHPLC) for the analysis of genetic variations: impact for diagnostics and pharmacogenetics. Clin Chem Lab Med. 2003; 41(4):452-61. DOI: 10.1515/CCLM.2003.068. View

Newton Bishop J, Harland M, Bishop D . The genetics of melanoma: the UK experience. Clin Exp Dermatol. 1999; 23(4):158-61. DOI: 10.1046/j.1365-2230.1998.00344.x. View

van der Heiden I, van der Werf M, Lindemans J, van Schaik R . Sequencing: not always the "gold standard". Clin Chem. 2004; 50(1):248-9. DOI: 10.1373/clinchem.2003.024604. View

Holland E, Schmid H, Kefford R, Mann G . CDKN2A (P16(INK4a)) and CDK4 mutation analysis in 131 Australian melanoma probands: effect of family history and multiple primary melanomas. Genes Chromosomes Cancer. 1999; 25(4):339-48. View

Mantelli M, Barile M, Ciotti P, Ghiorzo P, Lantieri F, Pastorino L . High prevalence of the G101W germline mutation in the CDKN2A (P16(ink4a)) gene in 62 Italian malignant melanoma families. Am J Med Genet. 2002; 107(3):214-21. View

Kamb A, Eeles R, Liu Q, Gruis N, Ding W, Hussey C . Analysis of the p16 gene (CDKN2) as a candidate for the chromosome 9p melanoma susceptibility locus. Nat Genet. 1994; 8(1):23-6. DOI: 10.1038/ng0994-22. View

Hussussian C, Struewing J, Goldstein A, Higgins P, Ally D, Sheahan M . Germline p16 mutations in familial melanoma. Nat Genet. 1994; 8(1):15-21. DOI: 10.1038/ng0994-15. View

Harland M, Meloni R, Gruis N, Pinney E, Brookes S, Spurr N . Germline mutations of the CDKN2 gene in UK melanoma families. Hum Mol Genet. 1997; 6(12):2061-7. DOI: 10.1093/hmg/6.12.2061. View

10.

Gillanders E, Juo S, Holland E, Jones M, Nancarrow D, Freas-Lutz D . Localization of a novel melanoma susceptibility locus to 1p22. Am J Hum Genet. 2003; 73(2):301-13. PMC: 1180369. DOI: 10.1086/377140. View

11.

Bishop D, Demenais F, Goldstein A, Bergman W, Bishop J, Bressac-de Paillerets B . Geographical variation in the penetrance of CDKN2A mutations for melanoma. J Natl Cancer Inst. 2002; 94(12):894-903. DOI: 10.1093/jnci/94.12.894. View

12.

Soufir N, Lacapere J, Bertrand G, Matichard E, Meziani R, Mirebeau D . Germline mutations of the INK4a-ARF gene in patients with suspected genetic predisposition to melanoma. Br J Cancer. 2004; 90(2):503-9. PMC: 2409576. DOI: 10.1038/sj.bjc.6601503. View

13.

Ruas M, Peters G . The p16INK4a/CDKN2A tumor suppressor and its relatives. Biochim Biophys Acta. 1998; 1378(2):F115-77. DOI: 10.1016/s0304-419x(98)00017-1. View

14.

Platz A, Hansson J, Ringborg U . Screening of germline mutations in the CDK4, CDKN2C and TP53 genes in familial melanoma: a clinic-based population study. Int J Cancer. 1998; 78(1):13-5. DOI: 10.1002/(sici)1097-0215(19980925)78:1<13::aid-ijc3>3.0.co;2-#. View

15.

Gross E, Arnold N, Goette J, Schwarz-Boeger U, Kiechle M . A comparison of BRCA1 mutation analysis by direct sequencing, SSCP and DHPLC. Hum Genet. 1999; 105(1-2):72-8. DOI: 10.1007/s004399900092. View

16.

Zuo L, Weger J, Yang Q, Goldstein A, Tucker M, Walker G . Germline mutations in the p16INK4a binding domain of CDK4 in familial melanoma. Nat Genet. 1996; 12(1):97-9. DOI: 10.1038/ng0196-97. View

17.

Ruiz A, Puig S, Malvehy J, Lazaro C, Lynch M, Gimenez-Arnau A . CDKN2A mutations in Spanish cutaneous malignant melanoma families and patients with multiple melanomas and other neoplasia. J Med Genet. 2000; 36(6):490-3. PMC: 1734379. View

18.

Liu W, Smith D, Rechtzigel K, Thibodeau S, James C . Denaturing high performance liquid chromatography (DHPLC) used in the detection of germline and somatic mutations. Nucleic Acids Res. 1998; 26(6):1396-400. PMC: 147438. DOI: 10.1093/nar/26.6.1396. View

19.

Newton Bishop J, Harland M, Bennett D, Bataille V, Goldstein A, Tucker M . Mutation testing in melanoma families: INK4A, CDK4 and INK4D. Br J Cancer. 1999; 80(1-2):295-300. PMC: 2363010. DOI: 10.1038/sj.bjc.6690354. View

20.

Harland M, Holland E, Ghiorzo P, Mantelli M, Bianchi-Scarra G, Goldstein A . Mutation screening of the CDKN2A promoter in melanoma families. Genes Chromosomes Cancer. 2000; 28(1):45-57. View