Allele-specific amplification in cancer revealed by SNP array analysis

Area of Science:

• Genomics
• Cancer Biology
• Bioinformatics

Background:

• Genomic alterations like amplification, deletion, and loss of heterozygosity are key cancer indicators.
• High-resolution techniques are advancing the measurement of chromosomal copy number and mapping of loss-of-heterozygosity events.

Purpose of the Study:

• To develop a novel probe-level allele-specific quantitation procedure for SNP array data.
• To extract both copy number and allelotype information for allele-specific copy number analysis across the genome.
• To determine generalized genotypes of aberrant samples and infer parental chromosome copy number.

Main Methods:

• Utilized an expectation-maximization algorithm applied to a novel classification of SNP array probes.
• Developed a method to determine generalized genotypes at SNP sites and infer allele-specific copy number.
• Validated allele-specific copy number inferences using PCR experiments and demonstrated precise genotyping of normal samples.

Main Results:

• The method accurately determines allele-specific copy number, including the haplotype of amplified or deleted regions.
• Analysis of lung cancer samples revealed that amplifications are predominantly monoallelic.
• Demonstrated that specific parental chromosomes may be targeted for amplification.

Conclusions:

• The developed method provides a powerful tool for detailed genomic analysis of cancer.
• Findings suggest targeted amplification of specific parental chromosomes in cancer, potentially due to germline or somatic variations.
• An R software package is available for public use.