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Tumor Discovery MUTYH mutation in advanced rectal cancer with 5-FU resistance

Table 1. Summary of the previously reported cases of CRC with MUTYH mutations
Study Mutation Clinical presentation Treatment regimens Outcome
Current Case (2024) Homozygous Middle rectal adenocarcinoma CAPOX+panitumumab; Stable disease for 16 months with
c.934-2A>G (Stage IV) with bladder invasion FOLFIRI+bevacizumab; IROX IROX before disease progression
Miyaki et al. 28 c.934-2A>G Multiple adenomas Surgery+5-FU-based Disease-free survival for
CRC diagnosed at 40 years of age chemotherapy 18 months
Nielsen et al. 13 Y179C, G396D Advanced CRC with polyposis FOLFIRI+bevacizumab Stable disease for 12 months
Taki et al. 25 c.934-2A>G Rectal adenocarcinoma with local Surgery+XELOX+bevacizumab Progression-free survival of
invasion 10 months
Tao et al. 27 c.312C>A (Y104X) Advanced rectal cancer and 5-FU+leucovorin Rapid progression despite
recurrent polyps standard chemotherapy
Cleary et al. 23 Y179C, G396D Early-onset CRC and polyposis Surgery, observation Long-term survival after surgical
resection
Sampson et al. 29 G382D Advanced CRC with few polyps FOLFIRI Partial response followed by
disease progression
Abbreviations: CAPOX, XELOX: Capecitabine plus oxaliplatin; CRC: Colorectal cancer; IROX: Irinotecan plus oxaliplatin; FOLFIRI: Fluoropyrimidine,
leucovorin, irinotecan; 5-FU: fluoropyrimidine.

Figure 2. The patient’s CT scans at different stages of treatment. The first CT was obtained at the time of diagnosis. The subsequent CTs were obtained
after the first line of treatment (CAPOX with panitumumab), the second line of treatment (FOLFIRI with bevacizumab), and the third line of treatment
(IROX) were completed.
Abbreviations: CT: Computed tomography; CAPOX: Capecitabine plus oxaliplatin. FOLFIRI: Fluorouracil, Leucovorin, and Irinotecan; IROX: Irinotecan
and Oxaliplatin.

as c.934-2A>G21 are linked to CRC, disrupting splicing temporary disease control. Further studies are required to
and impairing DNA repair mechanisms. 25-27 elucidate the clinical significance of MUTYH mutations
and optimize therapeutic strategies.
The refractory response to fluoropyrimidine-based
therapies in pur patient highlights the challenges of 4. Conclusion
managing CRC associated with MUTYH mutations.
Fluoropyrimidine resistance may result from impaired This case report highlights the aggressive nature of CRC
DNA repair, as observed in other MUTYH-associated with a homozygous c.934-2A>G MUTYH mutation
CRCs (Table 1). The effectiveness of IROX in our patient and the challenges associated with treatment resistance.
Comprehensive genomic profiling was pivotal in guiding
demonstrates the potential of non-fluoropyrimidine therapy, emphasizing its importance in young patients
regimens in similar cases. with CRC.
Although targeted therapies for MUTYH-associated
CRC are limited, comprehensive genomic profiling can Acknowledgments
guide personalized treatment. In our patient, genomic We acknowledge our patient and family for permitting
insights informed the use of IROX, which provided us to publish this case report for mankind’s benefit. We

Volume 4 Issue 1 (2025) 122 doi: 10.36922/td.5164