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

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Abstract Colorectal cancer (CRC) is one of the most common causes of cancer mortality in the world. The incidence is related to increases with age and western dietary habits. Early detection through screening by colonoscopy has been proven to effectively reduce disease-related mortality. Currently, it is generally accepted that most colorectal cancers originate from adenomas. This is known as the "adenoma-carcinoma sequence", and several studies have shown that early detection and removal of adenomas can effectively prevent the development of colorectal cancer. The other two pathways for CRC development ...
Source: Medicina (Kaunas) - Category: Universities & Medical Training Authors: Tags: Medicina (Kaunas) Source Type: research
Case Summary: A 56-year-old man with a history of hypertension and hyperlipidemia was referred by gastroenterology for bleeding per rectum. Because of a family history of colon cancer, he had several prior colonoscopies, most recently 3 years ago, without evidence of pathology. His mother was diagnosed with colon cancer in her mid-40s. His current colonoscopy demonstrated a 2.4 × 1.5 cm cecal adenocarcinoma. Staging workup revealed no evidence of metastatic disease. Because of the patient’s family history, the specimen was further evaluated and found to have high microsatellite instabilit...
Source: Diseases of the Colon and Rectum - Category: Gastroenterology Tags: Resident’s Corner Source Type: research
CONCLUSIONS: The age of onset of sessile serrated adenomas/polyps varies, but the pattern is consistent with increasing methylation in the mucosa. Early negative colonoscopies predict a low risk of methylator cancers. See Video Abstract at
Source: Diseases of the Colon and Rectum - Category: Gastroenterology Tags: Original Contributions: Colorectal Cancer Source Type: research
Lynch Syndrome (LS) and familial adenomatous polyposis (FAP) represent the most prevalent inherited colorectal cancer syndromes. The key to reducing morbidity and mortality in affected individuals is prevention, and there is interest in chemopreventive agents that can either delay or prevent the need for procedural or surgical interventions. Sulindac is supported as a chemopreventive agent for the reduction of colorectal and duodenal polyps, as well as desmoids, in FAP. Aspirin has shown benefit in reducing polyp burden in LS.
Source: Seminars in Colon and Rectal Surgery - Category: Gastroenterology Authors: Source Type: research
(University of Texas M. D. Anderson Cancer Center) Colon polyps from patients with Lynch syndrome, a hereditary condition that raises colorectal cancer risk, display immune system activation well before cancer development, according to research from The University of Texas MD Anderson Cancer Center. The preclinical research challenges traditional models of cancer immune activation and suggests immunotherapy may be useful for colorectal cancer prevention in certain high-risk groups.
Source: EurekAlert! - Cancer - Category: Cancer & Oncology Source Type: news
ConclusionSquamous cell carcinomas have been described in Lynch syndrome and Muir-Torre syndrome in two studies and two case reports. This new case further supports a possible relationship between Lynch syndrome and squamous cell carcinoma.
Source: Hereditary Cancer in Clinical Practice - Category: Cancer & Oncology Source Type: research
Chemoprevention offers an attractive option to prevent the occurrence of cancer in high risk cancer syndromes, such as familial adenomatous polyposis (FAP) and Lynch syndrome. However, data, especially from clinical trials, is sparse. This presentation will review the state of art concepts of chemoprevention in regards to these hereditary GI cancer syndromes.Lynch Syndrome: In the randomized CAPP2 trial, 861 participants with Lynch syndrome took either daily aspirin (600 mg) or placebo for up to 4 years; the primary endpoint was the development of CRC (1). After a mean follow-up of 55.7 months, participants taking daily as...
Source: Cancer Research - Category: Cancer & Oncology Authors: Tags: Prevention Source Type: research
A 43-year-old man presented to his primary care physician in January 2013 for a routine comprehensive physical evaluation. On initial presentation, he reported feeling well with no complaints. Review of systems was negative. The patient denied any symptoms of constitutional weight loss, fatigue, pelvic pain, urinary symptoms, hematuria, or change in sexual function. His past medical history was significant for cutaneous lipomas, diverticulosis, and colon polyps, including a tubulovillous adenoma and a tubular adenoma removed during colonoscopies in 2004 and 2012, respectively (Fig.  1).
Source: Urology - Category: Urology & Nephrology Authors: Tags: Grand Rounds Source Type: research
CONCLUSIONS: Rectal studding may be a sign of MYH-associated polyposis and raises questions about the biology of abnormal base excision repair.
Source: Diseases of the Colon and Rectum - Category: Gastroenterology Tags: Original Contributions: Endoscopy Source Type: research
Conclusion: Overall, about 60% of patients with personal history of colon polyps or cancer seen in an academic cancer risk clinic underwent genetic testing. Regarding differences by race, we noted a trend toward fewer African Americans getting germline testing; however, the difference was not statistically significant. Among tested individuals, African Americans were significantly older. There were no differences in multigene panel versus single syndrome testing between races. Further investigation is required to determine reasons for lower genetic testing in African Americans at older ages, though these differences do not...
Source: Cancer Epidemiology Biomarkers and Prevention - Category: Cancer & Oncology Authors: Tags: Familial and Genetic Epidemiology: Poster Presentations - Proffered Abstracts Source Type: research
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