Germline mutations in lung cancer and personalized medicine

Excerpt

Marafie et al. [1] identified a rare germline NBN gene mutation by whole exome sequencing (WES) in a lung cancer survivor from a large family with various types of cancer. Actually, they found 3 siblings, who had lung cancer at age 55, 54 and 49, respectively. The proband, a 59 year-old heavy cigarette smoker female, was diagnosed with lung cancer at age 49, and her histopathologic report revealed an adenocarcinoma (ADCA) of the middle lobe. At genetic analysis, the proband was found to be a heterozygous carrier for a rare variant in NBN gene, termed c.93_94delTG, a two bases-deletion disrupting the protein function and considered pathogenic. Moreover, the proband had other variants in RAD50 and BRCA1 genes, which are currently considered of uncertain clinical significance. Among the 8 tested subjects, including a yet asymptomatic sister, 6 carried one or more of these variants in different combinations and in an heterozygous state. NBN (nibrin) encodes a member of the MRE11/RAD50 double-strand break repair complex, which is an integral component of the BRCA1-associated genome surveillance complex, responsible for double strand DNA damage repair. Heterozygous carriers of NBN 657del5 mutation showed an increased risk of developing various tumors. …