title: Frequent loss Xq25 on the inactive X chromosome in primary breast carcinomas is associated with tumor grade and axillary lymph node metastasis.
abstract: We previously applied arbitrarily primed polymerase chain reaction DNA fingerprinting to identify molecular genetic alterations in primary breast carcinomas. One of the most frequently observed fingerprint alterations was a reduction in the intensity of the MCG1-B2 band in 32% of tumors, indicating recurrent loss of X-chromosome segments. This article reports a mapping analysis of those chromosomal deletions. The subchromosomal origin of MCG1-B2 was determined to be the Xq25 chromosomal region. Loss of heterozygosity (LOH) analysis was carried out on 72 infiltrating ductal carcinomas with a panel of seven microsatellite markers spanning Xq25. The smallest common region of the X-chromosome deletions was mapped to between markers DXS8059 and DXS8009, with the highest LOH frequency of 52.4% at the DXS8098 locus. The LOH at DXS8098 was associated with larger tumor size (> 3 cm) (P = 0.048, Fisher exact test), higher histologic grade (P = 0.036, Fisher exact test), and axillary lymph node metastasis (P = 0.020, Fisher exact test). These results suggest that the Xq25 region harbors a putative tumor suppressor gene whose inactivation in breast cancer is associated with tumor progression and metastasis. LOH at this region, therefore, potentially could be used as a prognostic marker for disease development. One of the two X chromosomes is transcriptionally silent in women. The loss of the Xq25 region detected in this study occurred preferentially on the inactive X chromosome. This suggests that the putative tumor suppressor gene may escape X inactivation.
authors.affiliation: Burnham Institute, La Jolla, CA 92037, USA.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Piao
authors.forename: Sergei R
authors.initials: SR
authors.lastname: Malkhosyan
mesh_terms: D000483:Alleles; D001365:Axilla; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000235:genetics* / Q000473:pathology / Q000556:secondary*; D002872:Chromosome Deletion; D002874:Chromosome Mapping / Q000379:methods; D016172:DNA Fingerprinting / Q000379:methods; D004303:Dosage Compensation, Genetic; D016147:Genes, Tumor Suppressor; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D019656:Loss of Heterozygosity / Q000235:genetics; D008207:Lymphatic Metastasis; D018895:Microsatellite Repeats / Q000235:genetics; D016133:Polymerase Chain Reaction / Q000379:methods; D014960:X Chromosome / Q000235:genetics*
chemical_list: D005819:Genetic Markers