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Tumor Discovery

CASE REPORT
Biallelic MUTYH gene mutation resulting in

fluoropyrimidine-resistant advanced rectal
cancer: A case report

Tawasapon Thambamroong * and Chawanya Rabiltossaporn 2
1
1 Division of Medical Oncology, Department of Medicine, Phramongkutklao Hospital and College of
Medicine, Bangkok, Thailand
2 Medical Oncology Unit, Department of Medicine, Nakhon Pathom Hospital, Nakhon Pathom,
Thailand
(This article belongs to the Special Issue: Colorectal Cancer: Best Tools for Diagnosis to
Management Strategies)

Abstract

Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide and
the third most common cancer in Thailand. Approximately 2% – 5% of CRC cases
are associated with inherited cancer syndromes, whereas the majority is sporadic.
Herein, we have reported the case of a 32-year-old male with poorly differentiated
middle rectal adenocarcinoma (T4bN1M1, Stage IV) that was refractory to
fluoropyrimidine-based chemotherapy. Genetic profiling revealed a homozygous
*Corresponding author:
Tawasapon Thambamroong c.934-2A>G mutation in the MUTYH gene, which disrupted the DNA repair. Despite
(t.thambamroong@pmk.ac.th) palliative radiation (30 Gy in 10 fractions) and systemic therapies (capecitabine
plus oxaliplatin + panitumumab and fluorouracil, leucovorin, and irinotecan +
Citation: Thambamroong T,
Rabiltossaporn C. Biallelic bevacizumab), the disease progressed rapidly. Third-line therapy with Irinotecan
MUTYH gene mutation resulting in plus oxaliplatin demonstrated initial success (partial response). Eventually, disease
fluoropyrimidine-resistant advanced progression ensued. This report highlights the challenges of managing CRC caused
rectal cancer: A case report.
Tumor Discov. 2025;4(1):120-124. by biallelic MUTYH mutations and emphasizes the importance of comprehensive
doi: 10.36922/td.5164 genomic profiling for guiding therapeutic decisions. A review of similar cases in the
Received: October 15, 2024 literature is also presented.
1st revised: November 30, 2024
Keywords: Colorectal neoplasms; Colonic neoplasms; Rectal neoplasms; Colorectal
2nd revised: December 5, 2024
neoplasms; Hereditary non-polyposis; Antineoplastic agents; MUTYH
Accepted: December 11, 2024
Published online: December 27,
2024
1. Background
Copyright: © 2024 Author(s).
This is an Open-Access article Colorectal cancer (CRC) is a primary global health concern, accounting for > 9% of
distributed under the terms of the
1
Creative Commons Attribution cancer-related deaths annually. In Thailand, CRC is the third most common malignancy.
License, permitting distribution, Although most CRC cases are sporadic, 2% – 5% are hereditary and linked to genetic
and reproduction in any medium, syndromes, such as Lynch syndrome (LS) and familial adenomatous polyposis (FAP). 2
provided the original work is
properly cited. LS, which is caused by mutations in mismatch repair (MMR) genes such as MLH1,
Publisher’s Note: AccScience MSH2, MSH6, and PMS2, is associated with microsatellite instability (MSI) and early-
Publishing remains neutral with onset CRC. FAP, an autosomal dominant syndrome is caused by mutations in APC.
2-5
regard to jurisdictional claims in 2,6
published maps and institutional FAP is associated with the development of numerous polyps and a high risk of CRC.
affiliations. In contrast, MUTYH-associated polyposis (MAP) is an autosomal recessive syndrome

Volume 4 Issue 1 (2025) 120 doi: 10.36922/td.5164