Assessing copy number aberrations and copy-neutral loss-of-heterozygosity across the genome as best practice: An evidence-based review from the Cancer Genomics Consortium (CGC) working group for chronic lymphocytic leukemia

Kathy Chun, Gail D. Wenger, Alka Chaubey, D. P. Dash, Rashmi Kanagal-Shamanna, Sibel Kantarci, Ravindra Bharat Kolhe, Daniel L. Van Dyke, Lu Wang, Daynna J. Wolff, Patricia M. Miron

Research output: Contribution to journalReview article

1 Citation (Scopus)

Abstract

The prognostic role of cytogenetic analysis is well-established in B-cell chronic lymphocytic leukemia (CLL). Approximately 80% of patients have a cytogenetic aberration. Interphase FISH panels have been the gold standard for cytogenetic evaluation, but conventional cytogenetics allows detection of additional abnormalities, including translocations, complex karyotypes and multiple clones. Whole genome copy number assessment, currently performed by chromosomal microarray analysis (CMA), is particularly relevant in CLL for the following reasons: (1) copy number alterations (CNAs) represent key events with biologic and prognostic significance; (2) DNA from fresh samples is generally available; and (3) the tumor burden tends to be relatively high in peripheral blood. CMA also identifies novel copy number variants and copy-neutral loss-of-heterozygosity (CN-LOH), and can refine deletion breakpoints. The Cancer Genomics Consortium (CGC) Working Group for CLL has performed an extensive literature review to describe the evidence-based clinical utility of CMA in CLL. We provide suggestions for the integration of CMA into clinical use and list recurrent copy number alterations, regions of CN-LOH and mutated genes to aid in interpretation.

Original languageEnglish (US)
Pages (from-to)236-250
Number of pages15
JournalCancer Genetics
Volume228-229
DOIs
StatePublished - Dec 1 2018

Fingerprint

Loss of Heterozygosity
B-Cell Chronic Lymphocytic Leukemia
Microarray Analysis
Genomics
Practice Guidelines
Genome
Cytogenetics
Neoplasms
Cytogenetic Analysis
Interphase
Tumor Burden
Karyotype
Chromosome Aberrations
Clone Cells
DNA
Genes

Keywords

  • Chromosomal microarray analysis (CMA)
  • Chronic lymphocytic leukemia (CLL)
  • Copy number alterations (CNAs)
  • Copy-neutral loss-of-heterozygosity (CN-LOH)
  • Cytogenetics
  • Fluorescence in situ hybridization (FISH)

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Assessing copy number aberrations and copy-neutral loss-of-heterozygosity across the genome as best practice : An evidence-based review from the Cancer Genomics Consortium (CGC) working group for chronic lymphocytic leukemia. / Chun, Kathy; Wenger, Gail D.; Chaubey, Alka; Dash, D. P.; Kanagal-Shamanna, Rashmi; Kantarci, Sibel; Kolhe, Ravindra Bharat; Van Dyke, Daniel L.; Wang, Lu; Wolff, Daynna J.; Miron, Patricia M.

In: Cancer Genetics, Vol. 228-229, 01.12.2018, p. 236-250.

Research output: Contribution to journalReview article

Chun, Kathy ; Wenger, Gail D. ; Chaubey, Alka ; Dash, D. P. ; Kanagal-Shamanna, Rashmi ; Kantarci, Sibel ; Kolhe, Ravindra Bharat ; Van Dyke, Daniel L. ; Wang, Lu ; Wolff, Daynna J. ; Miron, Patricia M. / Assessing copy number aberrations and copy-neutral loss-of-heterozygosity across the genome as best practice : An evidence-based review from the Cancer Genomics Consortium (CGC) working group for chronic lymphocytic leukemia. In: Cancer Genetics. 2018 ; Vol. 228-229. pp. 236-250.
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abstract = "The prognostic role of cytogenetic analysis is well-established in B-cell chronic lymphocytic leukemia (CLL). Approximately 80{\%} of patients have a cytogenetic aberration. Interphase FISH panels have been the gold standard for cytogenetic evaluation, but conventional cytogenetics allows detection of additional abnormalities, including translocations, complex karyotypes and multiple clones. Whole genome copy number assessment, currently performed by chromosomal microarray analysis (CMA), is particularly relevant in CLL for the following reasons: (1) copy number alterations (CNAs) represent key events with biologic and prognostic significance; (2) DNA from fresh samples is generally available; and (3) the tumor burden tends to be relatively high in peripheral blood. CMA also identifies novel copy number variants and copy-neutral loss-of-heterozygosity (CN-LOH), and can refine deletion breakpoints. The Cancer Genomics Consortium (CGC) Working Group for CLL has performed an extensive literature review to describe the evidence-based clinical utility of CMA in CLL. We provide suggestions for the integration of CMA into clinical use and list recurrent copy number alterations, regions of CN-LOH and mutated genes to aid in interpretation.",
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AU - Wenger, Gail D.

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AB - The prognostic role of cytogenetic analysis is well-established in B-cell chronic lymphocytic leukemia (CLL). Approximately 80% of patients have a cytogenetic aberration. Interphase FISH panels have been the gold standard for cytogenetic evaluation, but conventional cytogenetics allows detection of additional abnormalities, including translocations, complex karyotypes and multiple clones. Whole genome copy number assessment, currently performed by chromosomal microarray analysis (CMA), is particularly relevant in CLL for the following reasons: (1) copy number alterations (CNAs) represent key events with biologic and prognostic significance; (2) DNA from fresh samples is generally available; and (3) the tumor burden tends to be relatively high in peripheral blood. CMA also identifies novel copy number variants and copy-neutral loss-of-heterozygosity (CN-LOH), and can refine deletion breakpoints. The Cancer Genomics Consortium (CGC) Working Group for CLL has performed an extensive literature review to describe the evidence-based clinical utility of CMA in CLL. We provide suggestions for the integration of CMA into clinical use and list recurrent copy number alterations, regions of CN-LOH and mutated genes to aid in interpretation.

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