title: MSH2 splice site mutation and endometrial cancer.
abstract: Hereditary nonpolyposis colorectal cancer (HNPCC) is an inherited syndrome of cancer susceptibility caused by germ line mutations of genes participating in mismatch repair (MMR). Carriers of MMR gene mutations have an increased risk of colorectal cancers and cancer of other organs. Tumors of the endometrium represent the most frequent extracolonic malignancies in HNPCC. It has been suggested that women harboring MMR gene mutations have a higher risk of endometrial cancer than of colon cancer. Here, we describe an HNPCC patient with early-onset endometrial cancer and a strong familial history of endometrial tumors who harbored a germ line MSH2 splice site mutation (IVS9_2A>G). This mutation was responsible for abnormal messenger RNA processing, leading to the introduction of a premature stop signal and to the expression of a truncated MSH2 protein. In addition, the same mutation was associated with loss of MSH2 protein expression, high microsatellite instability, and PTEN inactivation. Although a direct relationship between the endometrial cancer susceptibility and the MSH2 mutation we found cannot be established, our observations, consistent with the work of other authors, suggest the involvement of germ line MSH2 abnormalities in endometrial tumor development and support the case for endometrial cancer screening in women from HNPCC families.
authors.affiliation: Istituto di Medicina Clinica e Biotecnologie Applicate-Oncologia Medica, Centro Regionale Alta Specializzazione in Genetica Oncologica, Facoltà di Medicina e Chirurgia, Università Politecnica delle Marche, Via Tronto, Ancona 60020, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Bianchi
authors.forename: S
authors.initials: S
authors.lastname: Rosati
authors.forename: L
authors.initials: L
authors.lastname: Belvederesi
authors.forename: C
authors.initials: C
authors.lastname: Loretelli
authors.forename: R
authors.initials: R
authors.lastname: Catalani
authors.forename: A
authors.initials: A
authors.lastname: Mandolesi
authors.forename: R
authors.initials: R
authors.lastname: Bracci
authors.forename: I
authors.initials: I
authors.lastname: Bearzi
authors.forename: E
authors.initials: E
authors.lastname: Porfiri
authors.forename: R
authors.initials: R
authors.lastname: Cellerino
mesh_terms: D000230:Adenocarcinoma / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D001483:Base Sequence; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000150:complications / Q000235:genetics; D004252:DNA Mutational Analysis / Q000379:methods; D016889:Endometrial Neoplasms / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D005260:Female; D042822:Genomic Instability; D006801:Humans; D007150:Immunohistochemistry; D008969:Molecular Sequence Data; D051718:MutS Homolog 2 Protein / Q000235:genetics* / Q000378:metabolism; D010375:Pedigree; D017354:Point Mutation; D012323:RNA Processing, Post-Transcriptional; D022821:RNA Splice Sites / Q000235:genetics*
chemical_list: D022821:RNA Splice Sites; C497172:MSH2 protein, human; D051718:MutS Homolog 2 Protein