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Microsatellite analysis at 10q25-q26 in Sardinian patients with sporadic endometrial carcinoma : identification of specific patterns of genetic alteration

Palmieri, Giuseppe and Manca, Antonella and Cossu, Antonio and Ruiu, Giovanni and Pisano, Marina and Cherchi, Pier Luigi and Dessole, Salvatore and Pintus, Adriana and Massarelli, Giovannino and Tanda, Francesco and Pirastu, Mario (2000) Microsatellite analysis at 10q25-q26 in Sardinian patients with sporadic endometrial carcinoma : identification of specific patterns of genetic alteration. Cancer, Vol. 89 (8), p. 1773-1782. eISSN 1097-0142. Article.

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DOI: 10.1002/1097-0142(20001015)89:8<1773::AID-CNCR18>3.0.CO;2-H


BACKGROUND. Loss of heterozygosity (LOH) at chromosome 10q25-q26 has been reported previously in endometrial carcinoma (EC), suggesting the presence of tumor suppressor gene(s). Nevertheless, frequency of genome-wide microsatellite instability (MSI) has been demonstrated higher in EC than in other common malignancy, mostly due to defective DNA mismatch repair. The authors further evaluated the role of the chromosome 10q25-q26 in endometrial tumorigenesis as well as the clinical significance of any observed genetic alteration in sporadic EC. METHODS. Paired normal and tumor samples from 94 Sardinian patients with sporadic EC at various stages of disease were screened by polymerase chain reaction (PCR)–based microsatellite analysis. Genomic DNA was isolated from paraffin embedded tissues and amplified by PCR using microsatellite markers spanning approximately 14 cM at 10q25-q26. Microsatellite instability was studied at four loci mapping to different chromosomal locations. RESULTS. Thirty-two (34%) EC patients were found negative for genetic alterations within the 10q25-q26 region. Among the remaining 62 (66%) EC cases, the authors identified 1) a minimum consensus region of LOH of approximately 1 cM, between D10S610 and D10S542 markers; and 2) a subset of tumors with prevalence of instability at 10q25-q26 (10qMI +), as expression of the presence of a MSI + phenotype. CONCLUSIONS. The authors’ data establish the existence of significant correlations between disease stages and 10qMI + (with or without MSI +). However, longer follow-up and additional studies are required to define the clinical significance of these findings as prognostic factors. Moreover, the minimum region of LOH at 10q25-q26 will be further analyzed for identifying the putative tumor suppressor gene involved in EC pathogenesis.

Item Type:Article
ID Code:1392
Uncontrolled Keywords:Endometrial carcinoma (EC), polymerase chain reaction (PCR), chromosome 10q25-q26, loss of heterozygosity (LOH), and microsatellite instability (MSI)
Subjects:Area 06 - Scienze mediche > MED/40 Ginecologia e ostetricia
Area 06 - Scienze mediche > MED/08 Anatomia patologica
Divisions:001 Università di Sassari > 03 Istituti > Anatomia patologica
001 Università di Sassari > 01 Dipartimenti > Neuroscienze, scienze materno infantili
002 Altri enti e centri di ricerca del Nord Sardegna > CNR-Consiglio Nazionale delle Ricerche > Istituto di genetica delle popolazioni, Alghero
Copyright Holders:© 2000 American Cancer Society
Deposited On:18 Aug 2009 10:05

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