Germline MUTYH gene mutations are not frequently found in unselected patients with papillary breast carcinoma

Ewout P Boesaard,Ingrid P Vogelaar,Carla Ap Wauters,Rachel S Van Der Post,Marjolijn Jl Ligtenberg,J Han Jm Van Krieken,Peter Bult,Nicoline Hoogerbrugge

doi:10.1186/1897-4287-12-21

Abstract

MUTYH-associated polyposis (MAP) is an autosomal recessive disease, which predisposes to polyposis and colorectal cancer. There is a trend towards an increased risk of breast cancer in MAP patients, with a remarkable proportion of papillary breast cancers. To determine whether MUTYH mutations are associated with this specific and rare type of breast cancer, 53 unselected patients with papillary breast cancer were analyzed for founder mutations in the MUTYH gene. No germline mutations were identified, indicating that biallelic MUTYH mutations are not a frequent underlying cause for the development of papillary carcinomas of the breast.

Highlights

MUTYH-associated polyposis (MAP) is an autosomal recessive disease, which was first identified by El-Tassan et al in 2002 [1]
Patient samples The study group consisted of 74 patients with papillary carcinomas of the breast, including papillary ductal carcinoma in situ (DCIS), intraductal/intracystic papillary carcinomas and invasive papillary carcinomas, which were diagnosed between January 1990 and December 2012 in the Radboud university medical center, and between January 2002 and December 2012 in the Canisius Wilhelmina Hospital, Nijmegen
From 53 patients (73.6%), including 9 patients with a colorectal adenoma and 3 patients with a colon carcinoma, the quality of the isolated DNA was sufficient for further use in analysis of the three most common founder mutations in the Dutch population

Summary

Introduction

MUTYH-associated polyposis (MAP) is an autosomal recessive disease, which was first identified by El-Tassan et al in 2002 [1]. The MUTYH gene is involved in base excision repair (BER) preventing G:C → T:A conversions. These conversions are caused by oxidative damage forming 8-oxo-7,8-dihydro-2-deoxyguanosine (8-oxoG) resulting in a mis-incorporation of adenine that, if not repaired by MUTYH DNA glycosylase, could lead to a G:C → T:A conversion [5,6,7]. The occurrence of MUTYH mutations in patients with breast cancer has been examined. Some of these studies found a significant increase in MUTYH mutations in breast cancer patients, while others could not find this potential association. Out et al found that minor allele genotypes of several MUTYH variants showed a trend towards association with lobular BC histology [14], while Rennert et al found no differences for ductal or other BC histology type among 30 patients heterozygous for p.Gly396Asp or p.Tyr179Cys and 359 patients homozygous wild-type for these mutations [15]

Methods

Results

Conclusion