Case Report: Novel RPGRIP1L Gene Mutations Identified by Whole Exome Sequencing in a Patient With Multiple Primary Tumors

A 78 years old Chinese woman with five different cancer types and a family history of malignancy was the subject of this study. Pancreatic adenocarcinoma and gingival squamous cell carcinoma tissues were obtained from the patient and sequenced using Whole Exome Sequencing. Whole exome sequencing identified 20 mutation sites in six candidate genes. Sanger Sequencing was used for further validation. The results verified six mutations in three genes, OBSCN, TTN, and RPGRIP1L, in at least one cancer type. Immunohistochemistry was used to verify protein expression. mRNA expression analysis using The Cancer Genome Atlas database revealed that RPGRIP1L was highly expressed in several cancer types, especially in pancreatic adenocarcinoma, and correlated with patient survival and sensitivity to paclitaxel, probably through the TGF-beta signaling pathway. The newly identified somatic mutations in RPGRIP1L might contribute to pathogenesis in the patients. Protein conformation simulation demonstrated that the alterations had caused the binding pocket at position 708 to change from concave to convex, which could restrict contraction and extension, and interfere with the physiological function of the protein. Further studies are required to determine the implication of RPGRIP1L in this family and in multiple primary tumors.

Automated summary

This study focused on a 78-year-old Chinese woman with multiple cancer types, finding that the RPGRIP1L gene may be associated with various types of cancers, especially pancreatic adenocarcinoma, potentially affecting patient survival and sensitivity to paclitaxel via the TGF-beta signaling pathway.Further research is needed to determine the significance of RPGRIP1L in this family and in multiple primary tumors.