Germline Mutations in Cancer Predisposition Genes are Frequent in Sporadic Sarcomas.
Germline Mutations in Cancer Predisposition Genes are Frequent in Sporadic Sarcomas.
复制标题
DOI：
10.1038/s41598-017-10333-x
复制
发表时间：
2017-09-06
影响因子：
4.6
通讯作者：
Ngeow J
中科院分区：
文献类型：
--
作者：
Chan SH;Lim WK;Ishak NDB;Li ST;Goh WL;Tan GS;Lim KH;Teo M;Young CNC;Malik S;Tan MH;Teh JYH;Chin FKC;Kesavan S;Selvarajan S;Tan P;Teh BT;Soo KC;Farid M;Quek R;Ngeow J
肉瘤与遗传性癌症综合征的关联暗示了肉瘤发生的遗传倾向。然而，由于肉瘤的明显散发性质，很少有人注意到遗传易感性在散发性肉瘤中的作用。为了解决这一问题，我们进行了靶向基因组测序，以调查已知的癌症相关基因的生殖细胞突变的患病率在一个亚洲队列的散发性肉瘤患者年龄小于50岁。我们观察到66例患者中有13.6%（n = 9）在10个癌症相关基因中至少有一个预测的致病性种系突变，包括ATM，BRCA 2，ERCC 4，FANCC，FANCE，FANCI，MSH6，POLE，SDHA和TP 53。最常受影响的基因涉及DNA损伤修复途径，生殖系突变发生率为10.6%。我们的研究结果表明，遗传易感性在我们的亚洲散发性肉瘤队列中发挥的作用比预期的要大，因此临床医生应该意识到年轻肉瘤患者可能是癌症基因遗传突变的携带者，无论家族史如何，都应该考虑进行基因检测。DNA损伤修复基因中生殖系突变的流行意味着利用受损DNA修复导致的脆弱性的治疗策略可能是转化研究的有前途的领域。
Associations of sarcoma with inherited cancer syndromes implicate genetic predisposition in sarcoma development. However, due to the apparently sporadic nature of sarcomas, little attention has been paid to the role genetic susceptibility in sporadic sarcoma. To address this, we performed targeted-genomic sequencing to investigate the prevalence of germline mutations in known cancer-associated genes within an Asian cohort of sporadic sarcoma patients younger than 50 years old. We observed 13.6% (n = 9) amongst 66 patients harbour at least one predicted pathogenic germline mutation in 10 cancer-associated genes including ATM, BRCA2, ERCC4, FANCC, FANCE, FANCI, MSH6, POLE, SDHA and TP53. The most frequently affected genes are involved in the DNA damage repair pathway, with a germline mutation prevalence of 10.6%. Our findings suggests that genetic predisposition plays a larger role than expected in our Asian cohort of sporadic sarcoma, therefore clinicians should be aware of the possibility that young sarcoma patients may be carriers of inherited mutations in cancer genes and should be considered for genetic testing, regardless of family history. The prevalence of germline mutations in DNA damage repair genes imply that therapeutic strategies exploiting the vulnerabilities resulting from impaired DNA repair may be promising areas for translational research.
登录
查看更多内容
来自1,092个人基因组的遗传变异的综合图。
影响因子：
64.8
作者：
通讯作者：
--
DOI：
10.1038/gim.2013.73
发表时间：
2013-07
期刊：
Genetics in medicine : official journal of the American College of Medical Genetics
影响因子：
--
作者：
通讯作者：
--
影响因子：
14.9
作者：
Nookala, Ravi K.;Hussain, Shobbir;Pellegrini, Luca
通讯作者：
Pellegrini, Luca
影响因子：
30.8
作者：
BOURGERON, T;RUSTIN, P;ROTIG, A
通讯作者：
ROTIG, A
影响因子：
--
作者：
Burningham Z;Hashibe M;Spector L;Schiffman JD
通讯作者：
Schiffman JD