Identification of germline and somatic mutations in pancreatic adenosquamous carcinoma using whole exome sequencing

OBJECTIVES Pancreatic cancer is one of the most lethal malignancies worldwide. Pancreatic adenosquamous carcinoma (PASC) is a rare histological type of pancreatic carcinoma with a poor prognosis. The median survival time after diagnosis is less than one year. It is believed that the pathogenesis of PASC is different from pancreatic adenocarcinoma. In this study, we tried to reveal the intrinsic gene mutations associated with PASC through whole exome sequencing. METHODS Both cancerous and paracancerous tissues were collected from 12 pathologically diagnosed PASC patients. Their clinical characteristics were collected, and patient survival information was obtained through follow-up. The correlations between the mutations and clinical characteristics were analysed. RESULTS Germline mutations were identified in MAP3K1 (9 cases), PDE4DIP (7), BCR (7), ALK (6), USP6 (5), AR (4), HLA-A (4), SPEN (4), KMT2D (3), NUTM2B (3), ZFHX3 (3), and MN1 (3), while somatic mutations were found in TP53 (5), KRAS (3), HRNR (3), and OBSCN (3). Peripheral tissue invasion was associated with somatic mutations in KRAS (P= 0.0339). Additionally, there were significant correlations between lymphatic metastasis and germline mutations in USP6 (P= 0.0228) and somatic mutations in OBSCN and HRNR (P= 0.0339). CONCLUSION In conclusion, susceptibility genes including MAP3K1, PDE4DIP, and BCR are frequently found to be mutated in the germlines of PASC patients. Somatic mutations in KRAS, OBSCN, and HRNR and germline mutations in USP6 are related to tumour invasion and metastasis, reinforcing the necessity of translating these potential biomarkers into clinical practice.