Cargando…

Chinese Pedigree with Hereditary Gastrointestinal Stromal Tumors: A Case Report and Literature Review

Familial gastrointestinal stromal tumor (GIST) is a rare autosomal dominant genetic disorder with only a few affected families reported to date. Here, we report a case of familial GISTs harboring a novel germline mutation within exon 18 of KIT. A 58-year-old male patient presented with gastric subep...

Descripción completa

Detalles Bibliográficos
Autores principales: Ge, Qichao, Liu, Yang, Yang, Fan, Sun, Guangwei, Guo, Jintao, Sun, Siyu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9820900/
https://www.ncbi.nlm.nih.gov/pubmed/36614290
http://dx.doi.org/10.3390/ijms24010830
_version_ 1784865570715336704
author Ge, Qichao
Liu, Yang
Yang, Fan
Sun, Guangwei
Guo, Jintao
Sun, Siyu
author_facet Ge, Qichao
Liu, Yang
Yang, Fan
Sun, Guangwei
Guo, Jintao
Sun, Siyu
author_sort Ge, Qichao
collection PubMed
description Familial gastrointestinal stromal tumor (GIST) is a rare autosomal dominant genetic disorder with only a few affected families reported to date. Here, we report a case of familial GISTs harboring a novel germline mutation within exon 18 of KIT. A 58-year-old male patient presented with gastric subepithelial lesions accompanied by cutaneous hyperpigmentation, which were subsequently diagnosed as multinodular GISTs. Endoscopic surgery was initially conducted to remove the larger lesions, and pathological examinations were then conducted for the diagnosis of GISTs. Family history revealed that some other family members had similar cutaneous pigmentations. Whole-exome sequencing was used to search for potential driver mutations, and Sanger sequencing was used for mutation validation. A novel primary driver mutation of KIT (c.G2485C, p.A829P) was detected in these hereditary GISTs, which has been reported in some targeted chemotherapy-resistant GISTs. Cell models were subsequently established for the rapid screening of candidate drugs and exploring potential mechanisms. This mutation could lead to cell proliferation and imatinib resistance by ligand-independent activation of KIT; however, ripretinib administration was identified as an applicable targeted therapy for this mutation. The mutation activated the JAK/STAT3 and MAPK/ERK pathways, which could be inhibited by ripretinib administration. To the best of our knowledge, this is the first report of the KIT-A829P mutation in familial GISTs, complementing the pathogenesis of familial GISTs and providing valuable information for the precision treatment of this disease.
format Online
Article
Text
id pubmed-9820900
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-98209002023-01-07 Chinese Pedigree with Hereditary Gastrointestinal Stromal Tumors: A Case Report and Literature Review Ge, Qichao Liu, Yang Yang, Fan Sun, Guangwei Guo, Jintao Sun, Siyu Int J Mol Sci Case Report Familial gastrointestinal stromal tumor (GIST) is a rare autosomal dominant genetic disorder with only a few affected families reported to date. Here, we report a case of familial GISTs harboring a novel germline mutation within exon 18 of KIT. A 58-year-old male patient presented with gastric subepithelial lesions accompanied by cutaneous hyperpigmentation, which were subsequently diagnosed as multinodular GISTs. Endoscopic surgery was initially conducted to remove the larger lesions, and pathological examinations were then conducted for the diagnosis of GISTs. Family history revealed that some other family members had similar cutaneous pigmentations. Whole-exome sequencing was used to search for potential driver mutations, and Sanger sequencing was used for mutation validation. A novel primary driver mutation of KIT (c.G2485C, p.A829P) was detected in these hereditary GISTs, which has been reported in some targeted chemotherapy-resistant GISTs. Cell models were subsequently established for the rapid screening of candidate drugs and exploring potential mechanisms. This mutation could lead to cell proliferation and imatinib resistance by ligand-independent activation of KIT; however, ripretinib administration was identified as an applicable targeted therapy for this mutation. The mutation activated the JAK/STAT3 and MAPK/ERK pathways, which could be inhibited by ripretinib administration. To the best of our knowledge, this is the first report of the KIT-A829P mutation in familial GISTs, complementing the pathogenesis of familial GISTs and providing valuable information for the precision treatment of this disease. MDPI 2023-01-03 /pmc/articles/PMC9820900/ /pubmed/36614290 http://dx.doi.org/10.3390/ijms24010830 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Case Report
Ge, Qichao
Liu, Yang
Yang, Fan
Sun, Guangwei
Guo, Jintao
Sun, Siyu
Chinese Pedigree with Hereditary Gastrointestinal Stromal Tumors: A Case Report and Literature Review
title Chinese Pedigree with Hereditary Gastrointestinal Stromal Tumors: A Case Report and Literature Review
title_full Chinese Pedigree with Hereditary Gastrointestinal Stromal Tumors: A Case Report and Literature Review
title_fullStr Chinese Pedigree with Hereditary Gastrointestinal Stromal Tumors: A Case Report and Literature Review
title_full_unstemmed Chinese Pedigree with Hereditary Gastrointestinal Stromal Tumors: A Case Report and Literature Review
title_short Chinese Pedigree with Hereditary Gastrointestinal Stromal Tumors: A Case Report and Literature Review
title_sort chinese pedigree with hereditary gastrointestinal stromal tumors: a case report and literature review
topic Case Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9820900/
https://www.ncbi.nlm.nih.gov/pubmed/36614290
http://dx.doi.org/10.3390/ijms24010830
work_keys_str_mv AT geqichao chinesepedigreewithhereditarygastrointestinalstromaltumorsacasereportandliteraturereview
AT liuyang chinesepedigreewithhereditarygastrointestinalstromaltumorsacasereportandliteraturereview
AT yangfan chinesepedigreewithhereditarygastrointestinalstromaltumorsacasereportandliteraturereview
AT sunguangwei chinesepedigreewithhereditarygastrointestinalstromaltumorsacasereportandliteraturereview
AT guojintao chinesepedigreewithhereditarygastrointestinalstromaltumorsacasereportandliteraturereview
AT sunsiyu chinesepedigreewithhereditarygastrointestinalstromaltumorsacasereportandliteraturereview