Abstract
Comprehensive genomic characterizations of lung squamous cell carcinoma (LSCC) have been performed, but the differences between smokers (S-LSCC) and never smokers (NS-LSCC) are not clear, as NS-LSCC could be considered as a different disease from S-LSCC. In this study we delineated genomic alterations in a cohort of 21 NS-LSCC and 16 S-LSCC patients, and identified common gene mutations and amplifications as previously reported. Inclusion of more NS-LSCC patients enabled us to identify unreported S-LSCC- or NS-LSCC-specific alterations. Importantly, an amplification region containing FGF19, FGF3, FGF4 and CCND1 was found five-times more frequent in S-LSCC than in NS-LSCC. Amplification of FGF19 was validated in independent LSCC samples. Furthermore, FGF19 stimulated LSCC cell growth in vitro. These data implicate FGF19 as a potential driver gene in LSCC with clinic characteristics as smoking.
Highlights
Lung cancer is the most frequent cause of cancer incidence and mortality worldwide
Twenty-one NS-lung squamous cell carcinoma (LSCC) patients were enrolled in Shanghai Chest Hospital from April 2009 to December 2012, while 16 S-LSCC patients were included in our study (Table 1; Supplementary Table S1)
Individuals display a mean point mutation rate of 3.88 mutations per megabase (Mb) and a median of 3.49 per Mb. This rate is higher than those observed in TCGA projects including acute myelogenous leukemia (0.56 per Mb), breast carcinoma (0.56 per Mb), ovarian cancer (2.1 per Mb) and glioblastoma multiforme (2.3 per Mb); but lower than rates observed in the TCGA LSCC project (8.1 per Mb) [6] and the Korean LSCC study (8.7 per Mb) [7]
Summary
Lung cancer is the most frequent cause of cancer incidence and mortality worldwide. After adenocarcinoma, lung squamous cell carcinoma (LSCC) is the second most common type of lung cancer. No targeted drug is approved for the treatment of LSCC largely due to the lack of knowledge of its molecular pathogenesis. Cigarette smoking is regarded as the most important risk factor for lung cancer, especially for LSCC (accounting for at least 90% patients) [1, 2]. An increasing number of ‘never smokers’ were being diagnosed with lung cancer, in which adenocarcinoma was the most common form [3]. Clinicopathological and molecular differences in lung adenocarcinomas arising in never smokers and in smokers were reported [4]. LSCC in never smokers (NS-LSCC) should be considered as a different disease than those in smokers (S-LSCC) [3, 5] Both the TCGA [6] and Korean [7] studies had characterized LSCC by integrative and comparative genomics approaches. Current knowledge of molecular profiles of NS-LSCC is lacking
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