Identification and validation of PROM1 and CRTC2 mutations in lung cancer patients

Weimin Li,Qian Huang,Yangkun Luo,Bin Zhou,Yalun Li,Shaoqin Shi,Zhixin Qiu,Kui Zhang,Yanqi He

doi:10.1186/1476-4598-13-19

Abstract

BackgroundGenetic alterations could be responsible lung cancer, the leading cause of worldwide cancer death.MethodsThis study investigated gene mutations in a Han Chinese family of lung cancer using the whole genome exome sequencing and subsequent Sanger sequencing validation and then confirmed alteration of prominin 1(PROM1) and cyclic AMP-response element binding protein-regulated transcription co-activator2 (CRTC2) in blood samples of 343 sporadic lung cancer patients vs. 280 healthy controls as well as in 200 pairs of lung cancer and the corresponding normal tissues using PCR-restriction fragment length polymorphism and directed DNA sequencing of PCR products.ResultsThe data showed PROM1 (p. S281R) and CRTC2 (p. R379C) mutations, in 5 and 2 cases of these 343 sporadic lung cancer patients, respectively. Notably, these mutations were absent in the healthy controls. Furthermore, in the 200 lung cancer and the matched normal tissues, PROM1 mutation occurred in 3 patients (i.e., one squamous cell carcinoma and two adenocarcinomas) with a mutation frequency of 1.5%, while CRTC2 mutation occurred in 5 patients (two squamous cell carcinomas and three adenocarcinomas) with a mutation frequency of 2.5%.ConclusionsThe data from the current study demonstrated novel PROM1 and CRTC2 mutations, which could promote lung cancer development.

Highlights

Genetic alterations could be responsible lung cancer, the leading cause of worldwide cancer death
Detection of prominin 1 (PROM1) T/G and cyclic AMP-response element binding protein-regulated transcription co-activator2 (CRTC2) G/A mutations in members of lung cancer family using whole genome Exome sequencing In this study, we performed whole genome Exome sequencing on genomic DNA samples of the four affected and unaffected relatives in this lung cancer family (Table 1)
To identify potential genetic variants associated with lung cancer development, we generated an average of 4.9 Gb of DNA sequence with 50X average coverage per individual as single-end, 90-bp reads and the fraction of effective bases on target was about 50% with a minimum 54-fold of average sequencing depth on the target

Summary

Introduction

Genetic alterations could be responsible lung cancer, the leading cause of worldwide cancer death. The overall five year survival rate of lung cancer remains approximately 15% worldwide, driven by the majority of cases diagnosed at advanced stages, resulting in non-resectable lesions [1]. Lung cancer can be aggregated in the family and inherited and appears to be the result of an interaction of multiple genes and environmental factors. Chromosomal region 15q2425.1, containing nicotinic acetylcholine receptor sub-unit genes, has been associated with increased risk of lung cancer in ever smokers [13,14]. Linkage analysis in families with aggregation of lung cancer showed a region on chromosome 6q23-25 associated with risk of lung cancer [15]. These data plus data among individuals with a family history of lung cancer indicate that the relative risk of lung cancer associated with markers in this region is much higher in familial cases compared to the relative risk observed among sporadic cases [16,17]

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Discussion

Conclusion