Lack of association between LOH in the 9p region and clinicopathologic parameters in primary breast cancer.
Previous studies have suggested the involvement of the 9p region in the genesis and progression of several types of cancer. To perform a more in-depth investigation of the 9p region in samples from breast carcinomas, we analyzed loss of heterozygosity (LOH) in 230 patients with primary breast cancer using five microsatellite markers spanning a genomic region of approximately 16.2 megabases. Genomic DNA was obtained from frozen tumor tissue, and peripheral blood was used as a normal reference. Among all samples, 171 (74%) were informative for at least 1 marker and 44 (25.73%) showed LOH. The LOH rates detected for all markers ranged from 10.29% (D9S169) to 15.97% (D9S1749). Among the informative cases for intragenic markers D9S1748 (CDKN2A) and D9S1749 (MTAP), we noticed a concordant loss of 90% (9/10). Associations between LOH frequencies and clinicopathologic parameters were found between marker D9S200 and tumor grade (P < 0.05), and between marker D9S1748 and estrogen receptor (ER) status (P < 0.05). In conclusion, our results agree with other data from the literature that point to LOH as a secondary mechanism of tumor suppressor inactivation on 9p in breast cancer, showing lower frequencies than those observed in other types of cancer. On the other hand, our results point to an interesting association between the concordant loss of genes CDKN2A and MTAP, which was not sufficiently explored in primary breast cancer.
Vieira de Oliveira
Sarah Franco
SF
Department of Genetics, Federal University of Paraná, Centro Politécnico, Jardim das Américas, Curitiba, PR, Brazil.
Oliveira
Márcia Maria Costa
MM
Urban
Cícero Andrade
CA
de Lima
Rubens Silveira
RS
Cavalli
Iglenir João
IJ
Ribeiro
Enilze Maria de Souza Fonseca
EM
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D002899:Chromosomes, Human, Pair 9; D005260:Female; D019942:Genes, p16; D006801:Humans; D019656:Loss of Heterozygosity; D008875:Middle Aged; D011683:Purine-Nucleoside Phosphorylase / Q000235:genetics; D011960:Receptors, Estrogen / Q000032:analysis
D011960:Receptors, Estrogen; D011683:Purine-Nucleoside Phosphorylase; C021784:5'-methylthioadenosine phosphorylase