Patient stratification for cancer therapy based on genomic DNA microarray analysis

摘要

The method of the invention comprises the stratification of a cancer patient population into various cancer therapy groups based on analysis by genomic DNA microarray of multiple gene amplifications or deletions present or absent in the diseased tissue of each patient. In particular, the invention involves patient stratification into one of at least four cancer therapy groups based on the microarray analysis of gene amplification or gene deletion at multiple chromosome locations.

主权项

1. A method of cancer patient stratification into one of at least four cancer therapy groups comprising:
(a) providing a diseased tissue or suspected disease tissue sample from a patient; (b) extracting chromosomal DNA from the tissue sample to produce a chromosomal DNA sample; (c) co-hybridizing the chromosomal DNA sample, labeled with a first fluorescent marker, and a reference DNA sample, labeled with a second fluorescent marker, to a nucleic acid microarray, said microarray comprising:
nucleic acid target elements from EGFR, AKT1, HER-2/neu, and TOPIIA attached to a solid support, wherein the nucleic acid target elements comprise polynucleotide sequences substantially complementary under preselected hybridization conditions to human genomic chromosomal DNA and wherein there is a sufficient number of said nucleic acid target elements to detect gene amplifications of EGFR, AKT1, HER-2/neu, and TOPIIA in the chromosomal DNA sample; (d) comparing a fluorescent ratio between colors of the first and second markers at a particular nucleic acid target element to provide a measurement of a copy number for genomic DNA sequences which are complementary to that nucleic acid target element; (e) stratifying the patient into one of the at least four cancer therapy groups selected from the group consisting of anti-HER-2/neu therapy, anti-EGFR therapy, anti-AKT1 therapy, anti-Topoisomerase II therapy, combination of anti-HER-2/neu therapy and anti-AKT1 therapy, and combination of anti-EGFR and anti-AKT1 therapy, based on presence or absence in at least one chromosomal gene amplification; and (f) performing a cancer therapy based on (e).