Clinical utility of array comparative genomic hybridization for detection of chromosomal abnormalities in pediatric acute lymphoblastic leukemia

Karen R. Rabin, Tsz Kwong Man, Alexander Yu, Matthew R. Folsom, Yi Jue Zhao, Pulivarthi H. Rao, Sharon E. Plon, Rizwan C. Naeem

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

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

Original languageEnglish (US)
Pages (from-to)171-177
Number of pages7
JournalPediatric Blood and Cancer
Volume51
Issue number2
DOIs
StatePublished - Aug 2008
Externally publishedYes

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Comparative Genomic Hybridization
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Chromosome Aberrations
Pediatrics
Karyotype
Fluorescence In Situ Hybridization
Cytogenetics
Bacterial Artificial Chromosomes
Bone Marrow

Keywords

  • Acute lymphoblastic leukemia (ALL)
  • Array comparative genomic hybridization (aCGH)

ASJC Scopus subject areas

  • Cancer Research
  • Pediatrics, Perinatology, and Child Health
  • Hematology
  • Medicine(all)

Cite this

Clinical utility of array comparative genomic hybridization for detection of chromosomal abnormalities in pediatric acute lymphoblastic leukemia. / Rabin, Karen R.; Man, Tsz Kwong; Yu, Alexander; Folsom, Matthew R.; Zhao, Yi Jue; Rao, Pulivarthi H.; Plon, Sharon E.; Naeem, Rizwan C.

In: Pediatric Blood and Cancer, Vol. 51, No. 2, 08.2008, p. 171-177.

Research output: Contribution to journalArticle

Rabin, Karen R. ; Man, Tsz Kwong ; Yu, Alexander ; Folsom, Matthew R. ; Zhao, Yi Jue ; Rao, Pulivarthi H. ; Plon, Sharon E. ; Naeem, Rizwan C. / Clinical utility of array comparative genomic hybridization for detection of chromosomal abnormalities in pediatric acute lymphoblastic leukemia. In: Pediatric Blood and Cancer. 2008 ; Vol. 51, No. 2. pp. 171-177.
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abstract = "Background. Accurate detection of recurrent chromosomal abnormalities is critical to assign patients to risk-based therapeutic regimens for pediatric acute lymphoblastic leukemia (ALL). Procedure. 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. Results. 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. aCCH 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. Conclusions. 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.",
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