A novel large germ line deletion in adenomatous polyposis coli (APC) gene associated with familial adenomatous polyposis.

Farzaneh Pouya,Kian Aminian Toosi,Seyed Abbas Tabatabaee Yazdi,Mohammad Amin Kerachian,Ghodratollah Soltani,Kamran Ghaffarzadegan,Afsaneh Mojtabanezhad Shariatpanahi,Hamed Golmohammadzadeh

doi:10.1002/mgg3.479

Abstract

BackgroundFamilial adenomatous polyposis (FAP) is a familial colorectal cancer predisposition syndrome characterized by the development of numerous colorectal polyps, which is inherited in an autosomal dominant manner. FAP is caused by germ line mutations in adenomatous polyposis coli (APC) gene. Here, we described the identification of a causative APC gene deletion associated with FAP in an Iranian family.MethodsDiagnosis of FAP was based on clinical findings, family history, and medical records (colonoscopy and histopathological data) after the patients were referred to Reza Radiotherapy and Oncology Center, Iran, for colonoscopy. Blood samples were collected, and genomic DNA was extracted. APC mutation screening was conducted by target next‐generation sequencing and quantitative real‐time PCR.ResultsA novel heterozygous large deletion mutation, c.(135+1_136–1)_(*2113+1_*2114–1) spanning exon 3 to 16 [EX3_16 DEL] of APC gene (GenBank Accession# MG712911), was detected in a proband and all her affected relatives in five generations, which was absent in unaffected family members and normal controls.ConclusionsThis novel deletion is the first report, describing the largest deletion of APC gene. Our novel finding contributes to a more comprehensive database of germ line mutations of APC gene that could be used in medical practice for the molecular diagnosis, risk assessment susceptibility of the disease for the FAP patients.

Highlights

Colorectal cancer (CRC), one of the major causes of morbidity and mortality, accounts for over 9% of all cancer incidences worldwide (Rokni, Shariatpanahi, Sakhinia, & Kerachian, 2018)
Familial adenomatous polyposis (FAP) [OMIM#175100] is a familial CRC syndrome marked by the development of numerous colorectal adenomas or polyps, which is inherited in an autosomal dominant manner
We identified a novel heterozygous large deletion, spanning exon 3 to 16 in adenomatous polyposis coli (APC) gene [NCBI Reference sequence NM_000038] in all the affected family members of a five‐generation Iranian family with FAP

Summary

| INTRODUCTION

Colorectal cancer (CRC), one of the major causes of morbidity and mortality, accounts for over 9% of all cancer incidences worldwide (Rokni, Shariatpanahi, Sakhinia, & Kerachian, 2018). Familial adenomatous polyposis (FAP) [OMIM#175100] is a familial CRC syndrome marked by the development of numerous colorectal adenomas or polyps, which is inherited in an autosomal dominant manner. Patients with AFAP manifest 10 to 100 adenomatous polyps, usually in an older age at diagnosis of both polyposis and CRC than in CFAP (Aretz et al, 2005; Knudsen, Bisgaard, & Bulow, 2003). FAP is caused by germ line mutations in adenomatous polyposis coli (APC) gene (Groden et al, 1991; Nishisho et al, 1991). APC is often cited as a typical example of a tumor suppressor gene and encodes a large multifunctional protein that plays an important role in the Wnt‐signaling pathway. Quantitative real‐time PCR (qPCR) was performed in order to segregate this germ line mutation in all affected members

| Ethical statement

| RESULTS

F DEL 72

Findings

| DISCUSSION