Identification of a rare germline NBN gene mutation by whole exome sequencing in a lung-cancer survivor from a large family with various types of cancer

AbstractNijmegen breakage syndrome is an autosomal recessive disorder caused by biallelic mutation inNBN gene. It is characterized by microcephaly, growth retardation, immuno-deficiency and cancer predisposition. The monoallelic carriers ofNBN gene are also reported to be at increased risk of developing various types of malignancy. We have investigated an individual with lung cancer from an extended family segregating different types of hereditary cancer over several generations, including lung, breast, ovarian, colon, prostate and renal cancers. By using next generation whole exome sequencing approach, we identified a rare heterozygous frameshift mutation inNBN gene; c.93_94delTG (Ala32HisfsTer4), which is predicted to be pathogenic together with 3 other variants; 2 being in theBRCA1 gene, c.1648A  >  C (p.Asn550His) and c.536A >  G (p.Tyr179Cys), and one inRAD50 gene, c.3539G  >  A (p.Arg1180Gln). Some of the variants were also found in six out of eight clinically normal relatives, but in different combinations. To our knowledge, this is the first report ofNBN gene mutation in an individual with lung cancer in the Arab world. Reporting such findings may aid in variants ’ risk classification and clinical decision in the future.
Source: Familial Cancer - Category: Cancer & Oncology Source Type: research