An Early-Onset Advanced Rectal Cancer Patient With Increased KRAS Gene Copy Number Showed A Primary Resistance to Cetuximab in Combination With Chemotherapy: A Case Report

Mutations in KRAS (codon 12/13), NRAS, BRAFV600E, and amplification of ERBB2 and MET account for 70–80% of anti-epidermal growth factor receptor (EGFR) monoclonal antibody primary resistance. However, the list of anti-EGFR monoclonal antibody primary resistance biomarkers is still incomplete. Herein...

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Autores principales:	Tian Fang, Tingting Liang, Yizhuo Wang, Haitao Wu, Shuhan Liu, Linying Xie, Zhihao Zhang, Jiaying Liang, Cheng Yao, Yehui Tan, Chang Wang
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	KRAS gene copy number colorectal cancer cetuximab case report anti-EGFR monoclonal antibody Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/641d4f9bb7764406b13f2d1505420918
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spelling	oai:doaj.org-article:641d4f9bb7764406b13f2d15054209182021-11-30T12:19:50ZAn Early-Onset Advanced Rectal Cancer Patient With Increased KRAS Gene Copy Number Showed A Primary Resistance to Cetuximab in Combination With Chemotherapy: A Case Report2234-943X10.3389/fonc.2021.755578https://doaj.org/article/641d4f9bb7764406b13f2d15054209182021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fonc.2021.755578/fullhttps://doaj.org/toc/2234-943XMutations in KRAS (codon 12/13), NRAS, BRAFV600E, and amplification of ERBB2 and MET account for 70–80% of anti-epidermal growth factor receptor (EGFR) monoclonal antibody primary resistance. However, the list of anti-EGFR monoclonal antibody primary resistance biomarkers is still incomplete. Herein, we report a case of wild-type RAS/BRAF metastatic colorectal cancer (CRC) with resistance to anti-EGFR monoclonal antibody and chemotherapy. Initially, mutation detection in postoperative tumor tissue by using amplification-refractory mutation system polymerase chain reaction indicated wild-type RAS/BRAF without point mutations, insertion deletions, or fusion mutations. Therefore, we recommended combined therapy of cetuximab and FOLFIRI after failure of platinum-based adjuvant chemotherapy, but the disease continued to progress. Next generation sequencing analysis of the postoperative tumor tissue revealed that KRAS copy number was increased and detected SMAD4, RNF43, and PREX2 mutations. This is the first case of advanced CRC with increased copy numbers of KRAS resistant to cetuximab and chemotherapy, which results in poor patient survival, and other mutated genes may be associated with the outcomes. Our findings indicate KRAS copy number alterations should also be examined, especially with anti-EGFR monoclonal antibody therapy in CRC, since it may be related with the primary resistance to these drugs.Tian FangTingting LiangYizhuo WangHaitao WuShuhan LiuLinying XieZhihao ZhangJiaying LiangCheng YaoYehui TanChang WangFrontiers Media S.A.articleKRASgene copy numbercolorectal cancercetuximabcase reportanti-EGFR monoclonal antibodyNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENFrontiers in Oncology, Vol 11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	KRAS gene copy number colorectal cancer cetuximab case report anti-EGFR monoclonal antibody Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	KRAS gene copy number colorectal cancer cetuximab case report anti-EGFR monoclonal antibody Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Tian Fang Tingting Liang Yizhuo Wang Haitao Wu Shuhan Liu Linying Xie Zhihao Zhang Jiaying Liang Cheng Yao Yehui Tan Chang Wang An Early-Onset Advanced Rectal Cancer Patient With Increased KRAS Gene Copy Number Showed A Primary Resistance to Cetuximab in Combination With Chemotherapy: A Case Report
description	Mutations in KRAS (codon 12/13), NRAS, BRAFV600E, and amplification of ERBB2 and MET account for 70–80% of anti-epidermal growth factor receptor (EGFR) monoclonal antibody primary resistance. However, the list of anti-EGFR monoclonal antibody primary resistance biomarkers is still incomplete. Herein, we report a case of wild-type RAS/BRAF metastatic colorectal cancer (CRC) with resistance to anti-EGFR monoclonal antibody and chemotherapy. Initially, mutation detection in postoperative tumor tissue by using amplification-refractory mutation system polymerase chain reaction indicated wild-type RAS/BRAF without point mutations, insertion deletions, or fusion mutations. Therefore, we recommended combined therapy of cetuximab and FOLFIRI after failure of platinum-based adjuvant chemotherapy, but the disease continued to progress. Next generation sequencing analysis of the postoperative tumor tissue revealed that KRAS copy number was increased and detected SMAD4, RNF43, and PREX2 mutations. This is the first case of advanced CRC with increased copy numbers of KRAS resistant to cetuximab and chemotherapy, which results in poor patient survival, and other mutated genes may be associated with the outcomes. Our findings indicate KRAS copy number alterations should also be examined, especially with anti-EGFR monoclonal antibody therapy in CRC, since it may be related with the primary resistance to these drugs.
format	article
author	Tian Fang Tingting Liang Yizhuo Wang Haitao Wu Shuhan Liu Linying Xie Zhihao Zhang Jiaying Liang Cheng Yao Yehui Tan Chang Wang
author_facet	Tian Fang Tingting Liang Yizhuo Wang Haitao Wu Shuhan Liu Linying Xie Zhihao Zhang Jiaying Liang Cheng Yao Yehui Tan Chang Wang
author_sort	Tian Fang
title	An Early-Onset Advanced Rectal Cancer Patient With Increased KRAS Gene Copy Number Showed A Primary Resistance to Cetuximab in Combination With Chemotherapy: A Case Report
title_short	An Early-Onset Advanced Rectal Cancer Patient With Increased KRAS Gene Copy Number Showed A Primary Resistance to Cetuximab in Combination With Chemotherapy: A Case Report
title_full	An Early-Onset Advanced Rectal Cancer Patient With Increased KRAS Gene Copy Number Showed A Primary Resistance to Cetuximab in Combination With Chemotherapy: A Case Report
title_fullStr	An Early-Onset Advanced Rectal Cancer Patient With Increased KRAS Gene Copy Number Showed A Primary Resistance to Cetuximab in Combination With Chemotherapy: A Case Report
title_full_unstemmed	An Early-Onset Advanced Rectal Cancer Patient With Increased KRAS Gene Copy Number Showed A Primary Resistance to Cetuximab in Combination With Chemotherapy: A Case Report
title_sort	early-onset advanced rectal cancer patient with increased kras gene copy number showed a primary resistance to cetuximab in combination with chemotherapy: a case report
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/641d4f9bb7764406b13f2d1505420918
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An Early-Onset Advanced Rectal Cancer Patient With Increased KRAS Gene Copy Number Showed A Primary Resistance to Cetuximab in Combination With Chemotherapy: A Case Report

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