Clinical utility of array comparative genomic hybridization for detection of chromosomal abnormalities in pediatric...

Accurate detection of recurrent chromosomal abnormalities is critical to assign patients to risk-based therapeutic regimens for pediatric acute lymphoblastic leukemia (ALL).

We investigated the utility of array comparative genomic hybridization (aCGH) for detection of chromosomal abnormalities compared to standard clinical evaluation with karyotype and fluorescent in situ hybridization (FISH). Fifty pediatric ALL diagnostic bone marrows were analyzed by bacterial artificial chromosome (BAC) array and findings compared to standard clinical evaluation.

Sensitivity of aCGH was 79% to detect karyotypic findings other than balanced translocations, which cannot be detected by aCGH because they involve no copy number change. aCGH also missed abnormalities occurring in subclones constituting less than 25% of cells. aCGH detected 44 additional abnormalities undetected or misidentified by karyotype with 21 subsequently validated by FISH, including abnormalities in 4 of 10 cases with uninformative cytogenetics. aCGH detected concurrent terminal deletions of both 9p and 20q in three cases, in two of which the 20q deletion was undetected by karyotype. A narrow region of loss at 7p21 was detected in two cases.

aCGH detects the majority of karyotypic findings other than balanced translocations, and may provide key prognostic information in the approximately 35% of cases with uninformative cytogenetics.