Familial Cancer

, Volume 6, Issue 1, pp 97–102

A missense germline mutation in exon 7 of the MSH2 gene in a HNPCC family from center-Italy

  • Francesca Bianchi
  • Eva Galizia
  • Emilio Porfiri
  • Laura Belvederesi
  • Romina Catalani
  • Cristian Loretelli
  • Raffaella Bracci
  • Italo Bearzi
  • Chiara Turchi
  • Alessandra Viel
  • Riccardo Cellerino
Original Paper

DOI: 10.1007/s10689-006-9110-z

Cite this article as:
Bianchi, F., Galizia, E., Porfiri, E. et al. Familial Cancer (2007) 6: 97. doi:10.1007/s10689-006-9110-z

Abstract

Introduction

Hereditary Non-Polyposis Colorectal Cancer (HNPCC) is an autosomal dominant inherited disease predisposing to the development of colorectal cancers and several other malignancies (endometrium, ovaries, stomach, small bowel, hepatobiliary and urinary tract). HNPCC is caused by germline mutations in any of the MisMatch Repair (MMR) genes. Mutations in MLH1 and MSH2 account for almost 90% of all identified ones. About 15% of mutations identified in MSH2 are missense ones.

Patients and methods

We studied one family, fulfilling Amsterdam II criteria, referred to our Center for genetic counselling. The proband, and some of her relatives, have been investigated for microsatellite instability (MSI), immunohistochemical MMR protein staining and by direct sequencing and Multiplex Ligation-dependent Probe Amplification (MLPA).

Results

All patients carried the same novel MSH2 germline missense mutation (R359S) in exon 7, which determines the substitution of an Arginine, which is a basic amino acid, with a polar Serine residue (R359S). The mutation was associated with lack of expression of MSH2 protein and high microsatellite instability in tumour tissues. The same mutation has been detected in one healthy relative.

Conclusions

The mutation here reported shows a high correlation with phenotype. The mutation is located in an evolutionary conserved domain. Taken together, our findings suggest evidence that the amino acid substitution can be interpreted as pathogenetic.

Keywords

Missense mutationsMSH2HNPCCEndometrial cancerColon cancer

Abbreviations

HNPCC

Hereditary Non-Polyposis Colorectal Cancer

MMR

MisMatch Repair

MSI

Microsatellite instability

IHC

Immunohistochemistry

InSiGHT

International Society for Gastrointestinal Hereditary Tumours

MLPA

Multiplex Ligation-dependent Probe Amplification

Copyright information

© Springer Science + Business Media B.V. 2006

Authors and Affiliations

  • Francesca Bianchi
    • 1
    • 2
  • Eva Galizia
    • 1
    • 2
  • Emilio Porfiri
    • 3
  • Laura Belvederesi
    • 1
    • 2
  • Romina Catalani
    • 1
    • 2
  • Cristian Loretelli
    • 1
    • 2
  • Raffaella Bracci
    • 1
    • 2
    • 4
  • Italo Bearzi
    • 5
  • Chiara Turchi
    • 6
  • Alessandra Viel
    • 7
  • Riccardo Cellerino
    • 1
    • 2
  1. 1.Istituto di Medicina Clinica e Biotecnologie Applicate-Oncologia MedicaUniversità Politecnica delle MarcheAnconaItaly
  2. 2.Centro Regionale di Alta Specializzazione in Genetica Oncologica, Facoltà di Medicina e ChirurgiaUniversità Politecnica delle MarcheAnconaItaly
  3. 3.Cancer Research-UK Institute for Cancer StudiesUniversity of BirminghamBirminghamUK
  4. 4.Clinica di Oncologia MedicaUniversità Politecnica delle MarcheAnconaItaly
  5. 5.Anatomia ed Istologia PatologicaUniversità Politecnica delle MarcheAnconaItaly
  6. 6.Dipartimento di Neuroscienze-Medicina LegaleUniversità Politecnica delle MarcheAnconaItaly
  7. 7.Oncologia Sperimentale 1, Dipartimento di Ricerca Preclinica ed EpidemiologicaCentro Riferimento Oncologico, IRCCSAvianoItaly