학술논문
Founder Mutations for Early Onset Melanoma as Revealed by Whole Exome Sequencing Suggests That This is Not Associated with the Increasing Incidence of Melanoma in Poland
Document Type
Article
Author
Tadeusz Debniak; Rodney J Scott; Rodney A Lea; Bohdan Górski; Bartlomiej Masojc; Cezary Cybulski; Andrzej Kram; Romuald Maleszka; Tomasz Gromowski; Katarzyna Paszkowska-Szczur; Aniruddh Kashyap; Marcin R. Lener; Karolina Malinska; Emilia Rogoza; Dawid Murawa; Helena Rudnicka; Jakub Deptula; Jan Lubinski
Source
Cancer Research and Treatment, 51(1), pp.337-344 Jan, 2019
Subject
Language
English
ISSN
2005-9256
1598-2998
1598-2998
Abstract
Purpose Germline mutations within melanoma susceptibility genes are present only in minority of melanoma patients and it is expected that additional genes will be discovered with next generation sequence technology and whole-exome sequencing (WES). Materials and Methods Herein we performed WES on a cohort of 96 unrelated Polish patients with melanoma diagnosed under the age of 40 years who all screened negative for the presence of CDKN2Avariants. A replication study using a set of 1,200 melanoma patient DNA samples and similarly large series of healthy controls was undertaken. Results We selected 21 potentially deleterious variants in 20 genes (VRK1, MYCT1, DNAH14, CASC3, MS4A12, PRC1, WWOX, CARD6, EXO5, CASC3, CASP8AP2, STK33, SAMD11, CNDP2, CPNE1, EFCAB6, CABLES1, LEKR1, NUDT17, and RRP15), which were identified by WES and confirmed by Sanger sequencing for an association study. Evaluation of the allele distribution among carriers and their relatives in available family trios revealed that these variants were unlikely to account for many familial cases of melanoma. Replication study revealed no statistically significant differences between cases and controls. Conclusion Although most of the changes seemed to be neutral we could not exclude an association between variants in VRK1, CREB3L3, EXO5, and STK33 with melanoma risk.