What question did this study set out to answer?

This case examines the rapid progression of colorectal cancer in a patient with combined MSI-H and EMAST features, focusing on genetic factors and implications for treatment.

April 5, 2026

Abstract 3685: A case of rapid progression from Stage I to Stage IV in an MSI-H/EMAST African American colorectal patient

Key Points

This case examines the rapid progression of colorectal cancer in a patient with combined MSI-H and EMAST features, focusing on genetic factors and implications for treatment.
Detailed patient history and clinical examination.
Colonoscopy to identify tumor and adenoma types.
Immunohistochemical analysis for specific markers.
Whole-genome sequencing for genetic variants and genomic instability.
STR profiling for microsatellite stability assessment.
Stage I adenocarcinoma progressed to stage IV with liver metastasis within one year.
Positive MSI-H and EMAST results indicated a unique genomic profile.
Diverse mutations and genomic instability patterns were identified through sequencing.
Significant intronic indel clusters indicated possible MutSβ dysfunction.
The case underscores the urgency of genetic counseling and targeted strategies.

Abstract

Abstract Colorectal cancer (CRC) remains a leading cause of cancer mortality. While most cases arise sporadically, familial risk contributes to about 30%, underscoring the need to assess family history during screening. Microsatellite instability (MSI) is a well-established diagnostic and prognostic biomarker, but elevated microsatellite alterations at selected tetranucleotide repeats (EMAST) remain poorly characterized, particularly among African American patients.We report a 59-year-old African American female with hypertension, hyperlipidemia, and congenital hearing and speech impairment who presented with rectal bleeding. Colonoscopy revealed a 7 cm mass in the transverse colon and a 15 mm sigmoid adenoma. Pathology confirmed a stage I (pT2N0M0) adenocarcinoma that rapidly progressed to stage IV with liver metastasis within one year. Immunohistochemistry showed loss of MLH1 and PMS2 with retained MSH2 and MSH6; MSI testing was MSI-high (BAT26), and EMAST was positive for RBM47.Whole-genome sequencing revealed dense intronic indel clusters in MSH3, suggesting MutSβ dysfunction consistent with EMAST. We also identified 21 deleterious missense variants across DNA-repair, immune, and transcriptional pathways (e.g., ZAP70, MSH4, ESR1, ACVR1B, LMNA). CNV gains were enriched in duplication-rich loci such as 11p15.5, 11q14, 13q31-q22, and 20q11-q13, overlapping oncogenic clusters (IGF2/H19, DNMT3B, SRC, BCL2L1, E2F1). Additionally, 19 frameshift and stop-gain mutations (e.g., GRIK2, NOS3, WNT16) introduced premature termination codons.STR profiling demonstrated bidirectional instability—18 expansions and 28 contractions across 46 intronic loci—confirming a pervasive EMAST pattern driven by MSH3 deficiency. This case illustrates a rare, aggressive MSI-H/EMAST CRC with rapid progression, extensive genomic instability, and dual MSI-EMAST features. Findings highlight the biological aggressiveness of combined MSI-H/EMAST tumors and emphasize the need for genetic counseling, molecular surveillance, and targeted precision strategies in underrepresented populations. Citation Format: Mudasir Rashid, Hassan Brim, Rabia Zafar, Christine Nembhard, Sudhir Varma, Hassan Ashktorab. A case of rapid progression from Stage I to Stage IV in an MSI-H/EMAST African American colorectal patient abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 3685.

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Cite This Study

Rashid et al. (Fri,) studied this question.

synapsesocial.com/papers/69d1fd29a79560c99a0a3095 https://doi.org/https://doi.org/10.1158/1538-7445.am2026-3685

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