Multi-gene panel testing confirms phenotypic variability in MUTYH -Associated Polyposis

We report the phenotypic spectrum of MAP in the context of multi-gene hereditary cancer panel testing. Genetic testing results and clinical histories were reviewed for individuals with biallelicMUTYH PVs detected by panel testing at a single commercial molecular diagnostic laboratory. BiallelicMUTYH PVs were identified in 82 individuals (representing 0.2% of tested individuals) with most (75/82; 91.5%) reporting a personal history of CRC and/or polyps. Ten percent (6/61) of individuals reporting polyp number reported fewer than 10 polyps and therefore did not meet current MAP testing criteria. Extracolonic cancers (21/82; 25.6%), multiple primaries (19/82; 23.2%), Lynch-like (17/82; 20.7%) and FAP-like phenotypes (16/82; 19.5%) were observed, including individuals with mismatch repair-deficient tumors (3/82; 3.7%), sebaceous neoplasms (2/82; 2.4%), or congenital hypertrophy of the retinal pigment epithelium (CHRPE) (2/82; 2.4%). We report what is to our knowledge the first cohort of individuals with MAP identified by panel testing. The phenotypic spectrum of MAP observed in this cohort aligns with the published literature. In addition to standard indications forMUTYH testing, our data provide evidence to support consideration of MAP in the differential diagnosis for some individuals with fewer than 10 polyps, depending on other personal and/or family history, as well as for individuals suspected to have Lynch syndrome or FAP.
Source: Familial Cancer - Category: Cancer & Oncology Source Type: research

Related Links:

Conclusions: The CRC stage and interval since last colonoscopy were not correlated, which is in conflict with the accelerated adenoma-carcinoma paradigm. We have previously reported that more frequent colonoscopy is not associated with lower incidence of CRC in path_MMR carriers as was expected. In contrast, point estimates showed a higher incidence with shorter intervals between examinations, a situation that may parallel to over-diagnosis in breast cancer screening. Our findings raise the possibility that some CRCs in path_MMR carriers may spontaneously disappear: the host immune response may not only remove CRC precurso...
Source: Clinical Genitourinary Cancer - Category: Cancer & Oncology Authors: Tags: Hered Cancer Clin Pract Source Type: research
ConclusionImmunohistochemical detection of colorectal polyp mismatch repair protein as Lynch syndrome screening efficiency is low. Effective screening strategies may be improved by optimizing patient/polyp selection, such as focusing on young adenoma patients with a family history of cancer, or patients who present with high-risk features (large size, villous, high-grade dysplasia and malignant components).
Source: Hereditary Cancer in Clinical Practice - Category: Cancer & Oncology Source Type: research
ConclusionsThe CRC stage and interval since last colonoscopy were not correlated, which is in conflict with the accelerated adenoma-carcinoma paradigm. We have previously reported that more frequent colonoscopy is not associated with lower incidence of CRC inpath_MMR carriers as was expected. In contrast, point estimates showed a higher incidence with shorter intervals between examinations, a situation that may parallel to over-diagnosis in breast cancer screening. Our findings raise the possibility that some CRCs inpath_MMR carriers may spontaneously disappear: the host immune response may not only remove CRC precursor le...
Source: Hereditary Cancer in Clinical Practice - Category: Cancer & Oncology Source Type: research
Abstract The molecular pathogenesis and classification of colorectal carcinoma are based on the traditional adenomaecarcinoma sequence, serrated polyp pathway, and microsatellite instability (MSI). The genetic basis for hereditary nonpolyposis colorectal cancer is the detection of mutations in the MLH1, MSH2, MSH6, PMS2, and EPCAM genes. Genetic testing for Lynch syndrome includes MSI testing, methylator phenotype testing, BRAF mutation testing, and molecular testing for germline mutations in MMR genes. Molecular makers with predictive and prognostic implications include quantitative multigene reverse transcriptas...
Source: Clinical Colorectal Cancer - Category: Cancer & Oncology Authors: Tags: Clin Lab Med Source Type: research
The molecular pathogenesis and classification of colorectal carcinoma are based on the traditional adenomaecarcinoma sequence, serrated polyp pathway, and microsatellite instability (MSI). The genetic basis for hereditary nonpolyposis colorectal cancer is the detection of mutations in the MLH1, MSH2, MSH6, PMS2, and EPCAM genes. Genetic testing for Lynch syndrome includes MSI testing, methylator phenotype testing, BRAF mutation testing, and molecular testing for germline mutations in MMR genes. Molecular makers with predictive and prognostic implications include quantitative multigene reverse transcriptase polymerase chain...
Source: Clinics in Laboratory Medicine - Category: Laboratory Medicine Authors: Source Type: research
This study assesses the relative frequency ofRNF43 mutations in hereditary colorectal cancers arising in the setting of Lynch syndrome. The entire coding region ofRNF43 was Sanger sequenced in 24 colorectal cancers from 23 patients who either (i) carried a germline mutation in one of the DNA mismatch repair genes (MLH1, MSH6, MSH2, PMS2), or (ii) showed immunohistochemical loss of expression of one or more of the DNA mismatch repair proteins, wasBRAF wild type at V600E, were under 60  years of age at diagnosis, and demonstrated no promoter region methylation forMLH1 in tumor DNA. A validation cohort of 44 colorectal c...
Source: Familial Cancer - Category: Cancer & Oncology Source Type: research
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
When I was first introduced to the concept of carcinogenesis as a medical student in 1969, the problem was conceptually a “black box”. Certain stimuli were carcinogenic, something happened to a cell, and cancer resulted. It had been noted in the beginning of the 20th Century that cancer cells had abnormal chromosomes (Boveri); it had been noted that chicken sarcomas could be transmitted by a “filterable agent” (Rous sarcoma virus); a variety of compounds could cause cancers on the skin of mice (chemical carcinogenesis), as well other physical agents (UV light, Xrays). There were other empirical obse...
Source: Cancer Research - Category: Cancer & Oncology Authors: Tags: Keynote Lectures Source Type: research
Conclusion Germline cancer susceptibility gene mutations are carried by 9.9% of patients with CRC. MSI/MMR testing reliably identifies LS probands, although 7.0% of patients with CRC carry non-LS mutations, including 1.0% with BRCA1/2 mutations. PMID: 28135145 [PubMed - as supplied by publisher]
Source: Clinical Colorectal Cancer - Category: Cancer & Oncology Authors: Tags: J Clin Oncol 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
More News: Cancer | Cancer & Oncology | Colorectal Cancer | Gastrointestinal Polyps | Gastroschisis Repair | Genetics | HNPCC | Laboratory Medicine | Lynch Syndrome | Polyps | Vitamin A