Dataset Information

Use of sanger and next-generation sequencing to screen for mosaic and intronic APC variants in unexplained colorectal polyposis patients.

ABSTRACT: In addition to classic germline APC gene variants, APC mosaicism and deep intronic germline APC variants have also been reported to be causes of adenomatous polyposis. In this study, we investigated 80 unexplained colorectal polyposis patients without germline pathogenic variants in known polyposis predisposing genes to detect mosaic and deep intronic APC variants. All patients developed more than 50 colorectal polyps, with adenomas being predominantly observed. To detect APC mosaicism, we performed next-generation sequencing (NGS) in leukocyte DNA. Furthermore, using Sanger sequencing, the cohort was screened for the following previously reported deep intronic pathogenic germline APC variants: c.1408 + 731C > T, p.(Gly471Serfs*55), c.1408 + 735A > T, p.(Gly471Serfs*55), c.1408 + 729A > G, p.(Gly471Serfs*55) and c.532-941G > A, p.(Phe178Argfs*22). We did not detect mosaic or intronic APC variants in the screened unexplained colorectal polyposis patients. The results of this study indicate that the deep intronic APC variants investigated in this study are not a cause of colorectal polyposis in this Dutch population. In addition, NGS did not detect any further mosaic variants in our cohort.

SUBMITTER: Elsayed FA

PROVIDER: S-EPMC8799582 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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Use of sanger and next-generation sequencing to screen for mosaic and intronic APC variants in unexplained colorectal polyposis patients.

Elsayed Fadwa A FA Tops Carli M J CMJ Nielsen Maartje M Morreau Hans H Hes Frederik J FJ van Wezel Tom T

Familial cancer 20210308 1

In addition to classic germline APC gene variants, APC mosaicism and deep intronic germline APC variants have also been reported to be causes of adenomatous polyposis. In this study, we investigated 80 unexplained colorectal polyposis patients without germline pathogenic variants in known polyposis predisposing genes to detect mosaic and deep intronic APC variants. All patients developed more than 50 colorectal polyps, with adenomas being predominantly observed. To detect APC mosaicism, we perfo ...[more]

PMID: 33683519

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Project description:Expression profiling is a well established tool for the genome-wide analysis of the transcriptional activity of human neoplasia. However, the high sensitivity of this approach combined with the well-known cellular and molecular heterogeneity of cancer often result in extremely complex and extended expression signatures of difficult functional interpretation. The majority of sporadic colorectal cancer cases are triggered by mutations in the APC tumor suppressor gene leading to constitutive activation of the Wnt/b-catenin signaling pathway and adenoma formation. Notwithstanding this common genetic basis, colorectal cancers are very heterogeneous in their degree of differentiation, growth rate and malignant potential. Here, we applied cross-species comparison of expression profiles of intestinal polyps derived from hereditary colorectal cancer patients carrying APC germline mutations, and from a mouse model carrying a targeted inactivating mutation in the mouse homologue Apc. This comparative approach resulted in the establishment of a conserved signature encompassing 166 genes differentially expressed between adenomas and normal intestinal mucosa in both species. Functional analysis of the conserved genes revealed a general increase in cell proliferation and the activation of the Wnt/b-catenin signal transduction pathway, as expected from the selection of APC/Apc-mutant intestinal adenomas. Moreover, the conserved signature is able to resolve expression profiles from hereditary polyposis patients carrying APC germline mutations from those with bi-allelic incativation of the MYH gene. Keywords: normal versus tumor comparison; compare expression profiles from microdissected samples with distinct germline mutations (FAP vs. MAP). Here, we report the expression profiles from normal and intestinal adenomatous tissue from FAP (familial adenomatous polyposis) and MAP (MUTY-associated polyposis) patients with established APC and MUTY germline mutations. Total RNA samples were obtianed by laser capture microdissection.

Dataset Information

Use of sanger and next-generation sequencing to screen for mosaic and intronic APC variants in unexplained colorectal polyposis patients.

Publications

Use of sanger and next-generation sequencing to screen for mosaic and intronic APC variants in unexplained colorectal polyposis patients.

Similar Datasets

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