e20511 Background: Smoking and air pollution are the major causes of lung cancer; however, numerous studies have demonstrated that genetic factors also contribute to the development of lung cancer. Here, we reported an analysis of genomic features in 65 lung cancer patients with autosomal-dominant or autosomal-recessive inheritance of germline mutations. Methods: We retrospectively reviewed next-generation sequencing data of 26,904 lung cancer patients in a Chinese cohort. The germline mutation patterns, as well as the co-occurrence with somatic driver mutations were analyzed. Results: A total of 65 (0.24%) patients with heterozygous germline mutations associated with hereditary cancer syndromes were detected, including 27 (0.10%) patients with autosomal-dominant inheritance (BRCA1, BRCA2, RET and TP53) and 38 (0.14%) patients with autosomal-recessive inheritance (ATM, BLM, FANCA, FANCG, MUTYH, NBN, RECQL4 and WRN). Comparing to patients with autosomal-dominant inheritance (Age 56±17.8), patients with autosomal-recessive inheritance (Age 65±11.7, P = 0.009) were older, and there is no gender difference. Additionally, 66.7% (18/27) of patients with autosomal-dominant inheritance were identified co-mutated actionable variations, such as 12 patients harboring mutations in exon 18–21 of EGFR, 2 patients harboring ERBB2 exon 20 insertions, 3 patients harboring mutations in exon 2 of KRAS and 1 patient harboring EML4-ALK fusion. The coexistence of germline autosomal-dominant mutations and somatic driver mutations indicated that germline mutations have weak impact on lung cancer. Simultaneously, 52.6% (20/38) of patients with autosomal-recessive inheritance were identified co-mutated actionable variations, such as 15 EGFR+ patients, 2 ERBB2+ patients and 3 KRAS+ patients. And there was no significant difference in population frequency of co-mutated actionable variations between the two groups. Conclusions: In summary, studies on germline mutations of lung cancer patients may help to elucidate the etiology and mechanism of lung cancer, and may help for early detection and diagnosis, targeted therapy and improved prevention strategies.
Short stature, brachydactyly, and Peters' anomaly (Peters'-plus syndrome): confirmation of autosomal recessive inheritance.
