Germline mutations causing familial lung cancer
Germline mutations causing familial lung cancer
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DOI：
10.1038/jhg.2015.75
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发表时间：
2015-10-01
影响因子：
3.5
通讯作者：
Nagayasu, Takeshi
中科院分区：
文献类型：
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作者：
Tomoshige, Koichi;Matsumoto, Keitaro;Nagayasu, Takeshi
遗传因素在肺癌中很重要，但由于大多数肺癌是散发性的，对遗传因素知之甚少。我们发现了一个三代人的家族，疑似常染色体显性遗传肺癌易感性。该家族中有16人患有肺癌。为了鉴定该家系中导致肺癌的基因，我们从三个个体的外周血和一个无癌症对照家庭成员的血液中提取DNA，并进行全外显子组测序。我们在所有受影响的家庭成员中发现了40个基因的41个变异，但未受影响的成员中没有。这些被认为是家族性肺癌的候选突变。接下来，为了鉴定散发性肺癌中这40个基因的体细胞突变和/或遗传性改变，我们使用来自散发性肺癌患者的192个样本进行了外显子靶富集测序。我们在多个散发性肺癌样本中检测到体细胞“候选”突变; MAST 1、CENPE、CACNB 2和LCT是最有希望的候选基因。此外，MAST 1基因位于一个假定的癌症连锁基因座的系谱。我们的数据表明，在这个家族中有几个基因作为致癌驱动因子，MAST 1最有可能导致肺癌。
Genetic factors are important in lung cancer, but as most lung cancers are sporadic, little is known about inherited genetic factors. We identified a three-generation family with suspected autosomal dominant inherited lung cancer susceptibility. Sixteen individuals in the family had lung cancer. To identify the gene(s) that cause lung cancer in this pedigree, we extracted DNA from the peripheral blood of three individuals and from the blood of one cancer-free control family member and performed whole-exome sequencing. We identified 41 alterations in 40 genes in all affected family members but not in the unaffected member. These were considered candidate mutations for familial lung cancer. Next, to identify somatic mutations and/or inherited alterations in these 40 genes among sporadic lung cancers, we performed exon target enrichment sequencing using 192 samples from sporadic lung cancer patients. We detected somatic 'candidate' mutations in multiple sporadic lung cancer samples; MAST1, CENPE, CACNB2 and LCT were the most promising candidate genes. In addition, the MAST1 gene was located in a putative cancer-linked locus in the pedigree. Our data suggest that several genes act as oncogenic drivers in this family, and that MAST1 is most likely to cause lung cancer.