Whole exome sequencing identifies driver mutations in asymptomatic computed tomography-detected lung cancers with normal karyotype

被引：9

作者：

Belloni, Elena ^{[1
,2
]}

Veronesi, Giulia ^{[3
]}

Rotta, Luca ^{[4
]}

Volorio, Sara ^{[6
,7
]}

Sardella, Domenico ^{[6
,7
]}

Bernard, Loris ^{[1
,7
]}

Pece, Salvatore ^{[1
,2
]}

Di Fiore, Pier Paolo ^{[1
,2
,5
,6
,9
]}

Fumagalli, Caterina ^{[8
]}

Barberis, Massimo ^{[6
,8
]}

Spaggiari, Lorenzo ^{[3
,9
]}

Pelicci, Pier Giuseppe ^{[1
,2
,9
]}

Riva, Laura ^{[10
]}

机构：

[1] European Inst Oncol, Dept Expt Oncol, Milan, Italy

[2] European Inst Oncol, Mol Med Care Program, Milan, Italy

[3] European Inst Oncol, Div Thorac Surg, Milan, Italy

[4] European Inst Oncol, Genom Unit, Milan, Italy

[5] Inst Mol Oncol Fdn IFOM, Federaz Italiana Ric Canc FIRC, Milan, Italy

[6] European Inst Oncol, Div Pathol, Milan, Italy

[7] Consortium Genom Technol Cogentech, Milan, Italy

[8] European Inst Oncol, Div Pathol, Milan, Italy

[9] Univ Milan, Dipartimento Sci Salute, Milan, Italy

[10] Fdn Ist Italian Tecnol, Ctr Genom Sci IIT SEMM, Milan, Italy

来源：

CANCER GENETICS | 2015年 / 208卷 / 04期

关键词：

CT-screening; normal karyotype; whole-exome sequencing; over-diagnosis; mutation instability in lung cancer; OVERDIAGNOSIS;

D O I：

10.1016/j.cancergen.2015.02.004

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The efficacy of curative surgery for lung cancer could be largely improved by non-invasive screening programs, which can detect the disease at early stages. We previously showed that 18% of screening-identified lung cancers demonstrate a normal karyotype and, following high-density genome scanning, can be subdivided into samples with 1) numerous; 2) none; and 3) few copy number alterations. Whole exome sequencing was applied to the two normal karyotype, screening-detected lung cancers, constituting group 2, as well as normal controls. We identified mutations in both tumors, including KEAP1 (commonly mutated in lung cancers) in one, and TP53, PMS1, and MSH3 (well-characterized DNA-repair genes) in the other. The two normal karyotype screening-detected lung tumors displayed a typical lung cancer mutational profile that only next generation sequencing could reveal, which offered an additional contribution to the over-diagnosis bias concept hypothesized within lung cancer screening programs.

引用

页码：152 / 155

页数：4

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