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Array Comparative Genomic Hybridization (Array CGH) for Detection of Genomic Copy Number Variants
Published on: February 21, 2015
High resolution array comparative genomic hybridization identifies copy number alterations in diffuse large B-cell
F Kreisel1, S Kulkarni, R T Kerns
1Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO, USA. fkreisel@path.wustl.edu
Cancer Genetics
|April 21, 2011
Summary
Genomic analysis reveals distinct DNA copy number alterations in diffuse large B-cell lymphoma (DLBCL) that predict chemotherapy response. These genetic markers could guide future DLBCL treatment strategies.
Area of Science:
- Genomics
- Oncology
- Molecular Biology
Background:
- Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous cancer with unclear prognostic biomarkers.
- Current sub-categorization methods like gene expression profiling do not fully resolve prognostic differences.
Purpose of the Study:
- To identify genetic differences, specifically DNA copy number alterations (CNAs), between chemoresistant and chemo-responsive DLBCL.
- To explore the potential of these CNAs as predictive biomarkers for R-CHOP therapy outcomes.
Main Methods:
- Whole genome, high-resolution array comparative genomic hybridization (aCGH) was performed on eight DLBCL cases (four chemoresistant, four chemo-responsive).
- Fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) were used to validate specific copy number losses, including tumor suppressor genes CDKN2A and CDKN2B.
Main Results:
- Seven CNA regions were exclusive to chemoresistant DLBCL, including amplifications at 1p36.13, 1q42.3, 3p21.31, 7q11.23, 16p13.3, and losses at 9p21.3 and 14p21.31.
- Twelve CNAs were detected in chemo-sensitive DLBCL, including gains on 1p36.11, 1p36.22, 2q11.2, 8q24.3, 12p13.33, 22q13.2, and loss on 6p21.32.
- Copy number loss of tumor suppressor genes CDKN2A and CDKN2B at 9p21.3 was confirmed in chemoresistant cases.
Conclusions:
- Whole genome aCGH successfully identified distinct CNAs associated with chemoresistance and chemo-responsiveness in DLBCL.
- These identified CNAs may serve as predictive biomarkers for prognosis and treatment outcomes in DLBCL patients receiving R-CHOP therapy.
