Novel germline mutation in lung cancer pedigrees establishes as a human cancer susceptibility gene: a case report.

BACKGROUND

Lung cancer is the most prevalent malignancy worldwide. Most cases are sporadic and carry somatic mutations in hotspot genes. However, accumulating studies have identified several germline mutations that predispose patients to lung cancer at present.

CASE DESCRIPTION

In this report, 2 siblings diagnosed with lung squamous cell carcinoma and lung adenocarcinoma were sequenced by whole exome sequencing (WES) and Sanger sequencing. In this context, we reported a novel frameshift germline mutation of breast cancer anti-estrogen resistance protein 1 () in exon 4 (NM_001170717: c.942delinsAATGCCAGGGC), causing a frameshift and introducing a premature stop codon, which was detected in both siblings. Screening across other family members revealed their presence in 2 affected individuals. The gene was previously demonstrated to be associated with lung cancer. The variant detected in this report would impair the regulation and functions of in some extent, thus may promote the tumorigenesis of lung cancer.

CONCLUSIONS

In conclusion, our findings suggest that is a possible susceptibility gene for lung cancer, and its functional analyses in lung cancer need further investigation. In this study, we first reported a novel causative mechanism of lung cancer: an insertion of 11 bp in gene, which can be helpful in the genetic diagnosis of this disease.