A t-statistic for objective interpretation of comparative genomic hybridization (CGH) profiles

An objective method for interpreting comparative genomic hybridization (CGH) is described and compared with current methods of interpretation. The method is based on a two-sample t-statistic in which composite test:reference and reference:reference CGH profiles are compared at each point along the genome to detect regions of significant differences. Composite profiles are created by combining CGH profiles measured from several metaphase chromosomes for each type of chromosome in the normal human karyotype. Composites for both test:reference and reference:reference CGH analyses are used to generate mean CGH profiles and information about the variance therein. The utility of the method is demonstrated through analysis of aneusomies and partial gain and loss of DNA sequence in a myeloid leukemia specimen. Banding analyses of this specimen indicated inv (3)(q21q26), del (5)(q2?q35), -7, +8 and add (17)(p11.2). The t-statistic analyses of CGH data indicated rev ish enh (8) and rev ish dim (5q31.1q33.1,7q11.23qter). The undetected gain on 17p was small and confined to a single band (17p11.2). Thus, the t-statistic is an objective and effective method for defining significant differences between test and reference CGH profiles.