Microsatellite analysis at 10q25-q26 in Sardinian patients with sporadic endometrial carcinoma: identification of specification patterns of genetic alteration.
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.
Palmieri
G
G
Institute of Molecular Genetics, C.N.R., Alghero, Italy. gpalmieri@yahoo.com
Manca
A
A
Cossu
A
A
Ruiu
G
G
Pisano
M
M
Cherchi
P
P
Dessole
S
S
Pintus
A
A
Massarelli
G
G
Tanda
F
F
Pirastu
M
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002874:Chromosome Mapping; D002879:Chromosomes, Human, Pair 10; D004273:DNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D005819:Genetic Markers; D006801:Humans; D007558:Italy; D019656:Loss of Heterozygosity; D018895:Microsatellite Repeats; D008875:Middle Aged; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction
D004273:DNA, Neoplasm; D005819:Genetic Markers