A Case of Microsatellite Instability–High Colon Cancer in a Young Woman With Familial Adenomatous Polyposis

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Steven M. Blum Dana-Farber Cancer Institute,
Massachusetts General Hospital, and

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William R. Jeck Brigham & Women’s Hospital, Boston, Massachusetts;
Duke University School of Medicine, Durham, North Carolina; and

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Lindsay Kipnis Dana-Farber Cancer Institute,

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Ronald Bleday Brigham & Women’s Hospital, Boston, Massachusetts;
Harvard Medical School, Boston, Massachusetts.

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Jonathan A. Nowak Dana-Farber Cancer Institute,
Brigham & Women’s Hospital, Boston, Massachusetts;
Harvard Medical School, Boston, Massachusetts.

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Matthew B. Yurgelun Dana-Farber Cancer Institute,
Brigham & Women’s Hospital, Boston, Massachusetts;
Harvard Medical School, Boston, Massachusetts.

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Two major molecular pathways of colorectal carcinogenesis, chromosomal instability (CIN) and microsatellite instability (MSI), are considered to be mutually exclusive. Distinguishing CIN from MSI-high tumors has considerable therapeutic implications, because patients with MSI-high tumors can derive considerable benefit from immune checkpoint inhibitors, and tumors that evolved through the CIN pathway do not respond to these agents. Familial adenomatous polyposis (FAP) is a genetic syndrome that is defined by a mutation in the APC gene and is thought to lead to carcinogenesis through the CIN pathway. Here, we report a case of a young woman with FAP who was treated for medulloblastoma as a child and developed advanced MSI-high colon cancer as a young adult. Her response to second-line immunotherapy enabled resection of her colon cancer, and she is free of disease >10 months after surgery. This case highlights the potential for overlap between the CIN and MSI carcinogenic pathways and associated therapeutic implications.

Submitted January 25, 2021; final revision received May 22, 2021; accepted for publication June 11, 2021.

Previous presentation: Preliminary data reported in this article were presented as a poster abstract at the 23rd Annual Meeting of the Collaborative Group of the Americas on Inherited Gastrointestinal Cancer; November 3–5, 2019; Salt Lake City, Utah.

Disclosures: Dr. Blum has disclosed serving as a consultant for Two River Consulting and Third Rock Ventures, and owning stock or having an ownership interest in Kronos Bio and Allogene Therapeutics. Dr. Yurgelun has disclosed receiving fees for peer review services from UpToDate. The authors have disclosed that they have not received any financial considerations from any person or organization to support the preparation, analysis, results, or discussion of this article.

Funding: Research reported in this publication was supported by the Massachusetts General Hospital T32 grant from the NCI of the NIH under award number 2T32CA071345-21A1 (S.M. Blum).

Disclaimer: The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

Correspondence: Matthew B. Yurgelun, MD, Dana-Farber Cancer Institute, 450 Brookline Avenue, Dana 1126, Boston, MA 02215. Email: matthew_yurgelun@dfci.harvard.edu

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