Tags

Type your tag names separated by a space and hit enter

Molecular genetic alterations and clinical features in early-onset colorectal carcinomas and their role for the recognition of hereditary cancer syndromes.
Am J Gastroenterol. 2005 Oct; 100(10):2280-7.AJ

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 demonstrates 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.

Authors+Show Affiliations

Department of Pathology, University of Modena and Reggio, Emilia, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16181381

Citation

Losi, Lorena, et al. "Molecular Genetic Alterations and Clinical Features in Early-onset Colorectal Carcinomas and Their Role for the Recognition of Hereditary Cancer Syndromes." The American Journal of Gastroenterology, vol. 100, no. 10, 2005, pp. 2280-7.
Losi L, Di Gregorio C, Pedroni M, et al. Molecular genetic alterations and clinical features in early-onset colorectal carcinomas and their role for the recognition of hereditary cancer syndromes. Am J Gastroenterol. 2005;100(10):2280-7.
Losi, L., Di Gregorio, C., Pedroni, M., Ponti, G., Roncucci, L., Scarselli, A., Genuardi, M., Baglioni, S., Marino, M., Rossi, G., Benatti, P., Maffei, S., Menigatti, M., Roncari, B., & Ponz de Leon, M. (2005). Molecular genetic alterations and clinical features in early-onset colorectal carcinomas and their role for the recognition of hereditary cancer syndromes. The American Journal of Gastroenterology, 100(10), 2280-7.
Losi L, et al. Molecular Genetic Alterations and Clinical Features in Early-onset Colorectal Carcinomas and Their Role for the Recognition of Hereditary Cancer Syndromes. Am J Gastroenterol. 2005;100(10):2280-7. PubMed PMID: 16181381.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Molecular genetic alterations and clinical features in early-onset colorectal carcinomas and their role for the recognition of hereditary cancer syndromes. AU - Losi,Lorena, AU - Di Gregorio,Carmela, AU - Pedroni,Monica, AU - Ponti,Giovanni, AU - Roncucci,Luca, AU - Scarselli,Alessandra, AU - Genuardi,Maurizio, AU - Baglioni,Silvana, AU - Marino,Massimiliano, AU - Rossi,Giuseppina, AU - Benatti,Piero, AU - Maffei,Stefania, AU - Menigatti,Mirco, AU - Roncari,Barbara, AU - Ponz de Leon,Maurizio, PY - 2005/9/27/pubmed PY - 2005/11/11/medline PY - 2005/9/27/entrez SP - 2280 EP - 7 JF - The American journal of gastroenterology JO - Am. J. Gastroenterol. VL - 100 IS - 10 N2 - 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 demonstrates 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. SN - 0002-9270 UR - https://www.unboundmedicine.com/medline/citation/16181381/Molecular_genetic_alterations_and_clinical_features_in_early_onset_colorectal_carcinomas_and_their_role_for_the_recognition_of_hereditary_cancer_syndromes_ L2 - http://Insights.ovid.com/pubmed?pmid=16181381 DB - PRIME DP - Unbound Medicine ER -