Molecular genetic alterations and clinical features in early-onset colorectal carcinomas and their role for the recognition of hereditary cancer syndromes

L Losi, Cristina Di Gregorio, M Pedroni, G Ponti, L Roncucci, A Scarselli, Maurizio Genuardi, S Baglioni, M Marino, G Rossi, P Benatti, S Maffei, M Menigatti, B Roncari, M de Leon

Risultato della ricerca: Contributo in rivistaArticolo in rivista

Abstract

OBJECTIVES: Colorectal cancer (CRC) occurs rarely in young individuals (< 45 yr) and represents one of the criteria for suspecting hereditary cancer families. In this study we evaluated clinical features and molecular pathways (chromosomal instability [CIN] and microsatellite instability [MSI]) in early-onset CRC of 71 patients. METHODS: Detailed family and personal history were obtained for each patient. Expression of APC, beta-catenin, p53, MLH1, MSH2, and MSH6 genes was evaluated by immunohistochemistry. MSI analysis was performed and constitutional main mutations of the mismatch repair (MMR) genes were searched by gene sequencing. RESULTS: Fourteen (19.7%) out of the 71 cases showed both MSI and altered expression of MMR proteins. In the 57 MSI-negative (MSI-) lesions altered expression of APC, beta-catenin, and p53 genes were found more frequently than in MSI-positive(MSI+) tumors. Seven (50%) out of the 14 patients with MSI+ tumors presented clinical features of Lynch syndrome (hereditary non-polyposis colorectal cancer [HNPCC]) and in all but one, constitutional mutations in MLH1 or MSH2 genes could be detected. The same mutations were also found in other family members. CONCLUSIONS: Our study demostrates the involvement of CIN in a majority of early-onset colorectal tumors. Furthermore, we identified Lynch syndromes in seven cases (50%) of early-onset colorectal carcinomas with impairment of the MMR system. These results suggest that patients with early-onset CRC should be screened for hereditary cancer syndrome through clinical and molecular characterizations.
Lingua originaleEnglish
pagine (da-a)2280-2287
Numero di pagine8
RivistaTHE AMERICAN JOURNAL OF GASTROENTEROLOGY
Volume100
DOI
Stato di pubblicazionePubblicato - 2005

Keywords

  • BETA-CATENIN
  • EXPRESSION
  • HMLH1 PROMOTER
  • K-RAS
  • MICROSATELLITE INSTABILITY
  • MISMATCH REPAIR GENES
  • MLH1 MUTATIONS
  • SPORADIC COLON-CANCER
  • TUMORS
  • YOUNG-PATIENTS

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