Genomewide scan for loss of heterozygosity and chromosomal amplification in breast carcinoma using single-nucleotide polymorphism arrays.
In an effort to identify novel genes implicated in breast carcinogenesis, a genomewide scan for loss of heterozygosity (LOH) and copy number changes in paired-DNA samples extracted from normal and tumor tissue of frozen sections from women undergoing surgery for invasive breast cancer was conducted. The Affymetrix 10K SNP array was used to examine genomewide LOH of chromosomal regions. The number of LOH events, number of informative loci, percent heterozygosity, and percent fractional allelic loss (%FAL) were calculated. Although LOH events were detected in all samples, the proportion of LOH ranged from 0.1 to 57.2%. Elevated LOH events were detected in two samples, with a %FAL of 57.2 and 56.2. Chromosomal regions exceeding a threshold value for a P-value curve based on multiple-testing adjusted permutation methods were identified as significant regions of shared LOH across samples. Regions with significant LOH included 2p25.3; 2p21; 2p15 approximately p16.1, 2q23.3; and, 16q12.1. Chromosomal region 1q32.1 was identified as a region with significant copy number amplification. Regions of LOH and copy number changes identified from this analysis may provide insights into the underlying processes of and genes involved in breast carcinogenesis. The present study demonstrates a feasible methodological approach for the assessment of LOH and copy number changes.
Argos
Maria
M
Department of Health Studies, University of Chicago, 5841 S. Maryland Avenue, MC 2007, Chicago, IL 60637, USA.
Kibriya
Muhammad G
MG
Jasmine
Farzana
F
Olopade
Olufunmilayo I
OI
Su
Tao
T
Hibshoosh
Hanina
H
Ahsan
Habibul
H
D001943:Breast Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D002869:Chromosome Aberrations; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics; D002887:Chromosomes, Human, Pair 18; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D005260:Female; D005784:Gene Amplification; D018628:Gene Dosage; D015894:Genome, Human; D006801:Humans; D019656:Loss of Heterozygosity / Q000235:genetics*; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*