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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 ide...

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Autores principales: Guo, Jiani, Yang, Yu, Ji, Zhuqing, Yao, Mengchu, Xia, Xiaotian, Sha, Xiaofeng, Huang, Mingde
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7882720/
https://www.ncbi.nlm.nih.gov/pubmed/33597970
http://dx.doi.org/10.3389/fgene.2021.620472
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author Guo, Jiani
Yang, Yu
Ji, Zhuqing
Yao, Mengchu
Xia, Xiaotian
Sha, Xiaofeng
Huang, Mingde
author_facet Guo, Jiani
Yang, Yu
Ji, Zhuqing
Yao, Mengchu
Xia, Xiaotian
Sha, Xiaofeng
Huang, Mingde
author_sort Guo, Jiani
collection PubMed
description 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-β 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.
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spelling pubmed-78827202021-02-16 Case Report: Novel RPGRIP1L Gene Mutations Identified by Whole Exome Sequencing in a Patient With Multiple Primary Tumors Guo, Jiani Yang, Yu Ji, Zhuqing Yao, Mengchu Xia, Xiaotian Sha, Xiaofeng Huang, Mingde Front Genet Genetics 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-β 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. Frontiers Media S.A. 2021-02-01 /pmc/articles/PMC7882720/ /pubmed/33597970 http://dx.doi.org/10.3389/fgene.2021.620472 Text en Copyright © 2021 Guo, Yang, Ji, Yao, Xia, Sha and Huang. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Genetics
Guo, Jiani
Yang, Yu
Ji, Zhuqing
Yao, Mengchu
Xia, Xiaotian
Sha, Xiaofeng
Huang, Mingde
Case Report: Novel RPGRIP1L Gene Mutations Identified by Whole Exome Sequencing in a Patient With Multiple Primary Tumors
title Case Report: Novel RPGRIP1L Gene Mutations Identified by Whole Exome Sequencing in a Patient With Multiple Primary Tumors
title_full Case Report: Novel RPGRIP1L Gene Mutations Identified by Whole Exome Sequencing in a Patient With Multiple Primary Tumors
title_fullStr Case Report: Novel RPGRIP1L Gene Mutations Identified by Whole Exome Sequencing in a Patient With Multiple Primary Tumors
title_full_unstemmed Case Report: Novel RPGRIP1L Gene Mutations Identified by Whole Exome Sequencing in a Patient With Multiple Primary Tumors
title_short Case Report: Novel RPGRIP1L Gene Mutations Identified by Whole Exome Sequencing in a Patient With Multiple Primary Tumors
title_sort case report: novel rpgrip1l gene mutations identified by whole exome sequencing in a patient with multiple primary tumors
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7882720/
https://www.ncbi.nlm.nih.gov/pubmed/33597970
http://dx.doi.org/10.3389/fgene.2021.620472
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