Identification of a novel GREM1 duplication in a patient with multiple colon polyps

AbstractHereditary mixed polyposis syndrome (HMPS) is a hereditary syndrome that is characterized by multiple colon polyps of mixed pathologic subtypes and an increased risk for colorectal cancer. A 40  kb duplication in the 5′ regulatory region of theGREM1 gene was recently found to be the causal mutation in a subset of Ashkenazi Jewish families with HMPS. Given this discovery, theGREM1 5 ′ regulatory region is now analyzed on many different multi-gene cancer panels, however the data on duplications distinct from the 40 kb duplication remains minimal. Herein we report a novel 24 kb tandem duplication of the 5′ regulatory region ofGREM1 in a patient without Ashkenazi Jewish heritage, who had a family history that was concerning for Lynch syndrome and satisfied Amsterdam II criteria. This is only the third reportedGREM1 duplication separate from the 40  kb Ashkenazi Jewish duplication, and is the only reported duplication to selectively involve exon 1 ofGREM1. This finding supports comprehensive testing of theGREM1 regulatory region in families of all ethnicities with multiple colon polyps or colon cancer, and when Lynch syndrome is suspected.
Source: Familial Cancer - Category: Cancer & Oncology Source Type: research