Expression and clinical significance of genes frequently mutated in small cell lung cancers defined by whole exome/RNA sequencing
Expression and clinical significance of genes frequently mutated in small cell lung cancers defined by whole exome/RNA sequencing
复制标题
DOI：
10.1093/carcin/bgv026
复制
发表时间：
2015-06-01
期刊：
影响因子：
4.7
通讯作者：
Yokota, Jun
中科院分区：
文献类型：
--
作者：
Iwakawa, Reika;Kohno, Takashi;Yokota, Jun
小细胞肺癌（SCLC）是最具侵袭性的肺癌类型。只有15%的SCLC患者在诊断后存活超过2年。因此，为了改善该疾病患者的预后，有必要确定适用于SCLC细胞的基因改变作为治疗靶点。本研究的目的是鉴定在SCLC中频繁突变和表达的基因，这些基因将为SCLC患者的治疗提供靶向性。对38例sclc患者的28例原发肿瘤和16例转移肿瘤进行外显子组测序。通过RNA测序验证了19例突变等位基因的表达。TP53、RB1和PTEN被鉴定为显著突变基因。结合本研究和最近的两项研究结果，另外36个基因在sclc中被确定为频繁突变（>= 10%）。在36个基因中，TMEM132D、SPTA1、VPS13B、CSMD2、ANK2、ASTN1、ASPM和FBN3中有8个基因表达突变等位基因。特别是TMEM132D、SPTA1和VPS13B基因在早期和晚期肿瘤、原发性肿瘤和转移性肿瘤以及化疗前后的肿瘤中都常见突变，TP53和RB1基因也是如此。因此，除了TP53、RB1和PTEN外，TMEM132D、SPTA1和VPS13B也可能参与SCLC的发展，其突变等位基因的产物可能是SCLC患者的潜在治疗靶点。
Small cell lung cancer (SCLC) is the most aggressive type of lung cancer. Only 15% of SCLC patients survive beyond 2 years after diagnosis. Therefore, for the improvement of patients' outcome in this disease, it is necessary to identify genetic alterations applicable as therapeutic targets in SCLC cells. The purpose of this study is the identification of genes frequently mutated and expressed in SCLCs that will be targetable for therapy of SCLC patients. Exome sequencing was performed in 28 primary tumors and 16 metastatic tumors from 38 patients with SCLCs. Expression of mutant alleles was verified in 19 cases by RNA sequencing. TP53, RB1 and PTEN were identified as being significantly mutated genes. Additional 36 genes were identified as being frequently (>= 10%) mutated in SCLCs by combining the results of this study and two recent studies. Mutated alleles were expressed in 8 of the 36 genes, TMEM132D, SPTA1, VPS13B, CSMD2, ANK2, ASTN1, ASPM and FBN3. In particular, the TMEM132D, SPTA1 and VPS13B genes were commonly mutated in both early and late stage tumors, primary tumors and metastases, and tumors before and after chemotherapy, as in the case of the TP53 and RB1 genes. Therefore, in addition to TP53, RB1 and PTEN, TMEM132D, SPTA1 and VPS13B could be also involved in SCLC development, with the products from their mutated alleles being potential therapeutic targets in SCLC patients.