Expression and clinical significance of genes frequently mutated in small cell lung cancers defined by whole exome/RNA sequencing

被引：67

作者：

Iwakawa, Reika ^{[1
]}

Kohno, Takashi ^{[1
,2
]}

Totoki, Yasushi ^{[3
]}

Shibata, Tatsuhiro ^{[3
]}

Tsuchihara, Katsuya ^{[2
]}

Mimaki, Sachiyo ^{[2
]}

Tsuta, Koji ^{[4
]}

Narita, Yoshitaka ^{[5
]}

Nishikawa, Ryo ^{[6
]}

Noguchi, Masayuki ^{[7
]}

Harris, Curtis C. ^{[8
]}

Robles, Ana I. ^{[8
]}

Yamaguchi, Rui ^{[9
]}

Imoto, Seiya ^{[9
]}

Miyano, Satoru ^{[9
]}

Totsuka, Hirohiko ^{[10
]}

Yoshida, Teruhiko ^{[11
]}

Yokota, Jun ^{[1
,12
]}

机构：

[1] Natl Canc Ctr, Res Inst, Div Genome Biol, Tokyo 1040045, Japan

[2] Natl Canc Ctr, Div Translat Res, Exploratory Oncol Res & Clin Trial Ctr, Tokyo 1040045, Japan

[3] Natl Canc Ctr, Res Inst, Div Canc Genom, Tokyo 1040045, Japan

[4] Natl Canc Ctr, Pathol Div, Tokyo 1040045, Japan

[5] Natl Canc Ctr, Dept Neurosurg & Neurooncol, Tokyo 1040045, Japan

[6] Saitama Med Univ, Dept Neurooncol Neurosurg, Int Med Ctr, Saitama 3501298, Japan

[7] Univ Tsukuba, Dept Pathol, Fac Med, Ibaraki 3058575, Japan

[8] NCI, Lab Human Carcinogenesis, NIH, Bethesda, MD 20892 USA

[9] Univ Tokyo, Inst Med Sci, Ctr Human Genome, Tokyo 1088639, Japan

[10] Hitachi Govt & Publ Corp Syst Engn Ltd, Solut Div 4, Ctr Res & Dev, Bioinfomat Grp, Tokyo 1358633, Japan

[11] Natl Canc Ctr, Res Inst, Div Genet, Tokyo 1040045, Japan

[12] Inst Predict & Personalized Med Canc, Canc Genome Biol Grp, Barcelona 08916, Spain

来源：

CARCINOGENESIS | 2015年 / 36卷 / 06期

关键词：

GENOMIC ANALYSIS; IDENTIFICATION; FRAMEWORK; HETEROGENEITY; METASTASES; TUMOR;

D O I：

10.1093/carcin/bgv026

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：616 / 621

页数：6

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