Reference Size Matching, Whole-Genome Amplification, and Fluorescent Labeling as a Method for Chromosomal Microarray Analysis of Clinically Actionable Copy Number Alterations in Formalin-Fixed, Paraffin-Embedded Tumor Tissue.
J Mol Diagn
; 20(3): 279-288, 2018 05.
Article
em En
| MEDLINE
| ID: mdl-29471114
ABSTRACT
Cancer genome copy number alterations (CNAs) assist clinicians in selecting targeted therapeutics. Solid tumor CNAs are most commonly evaluated in formalin-fixed, paraffin-embedded (FFPE) tissue by fluorescence in situ hybridization. Although fluorescence in situ hybridization is a sensitive and specific assay for interrogating preselected genomic regions, it provides no information about coexisting clinically significant copy number changes. Chromosomal microarray analysis is an alternative DNA-based method for interrogating genome-wide CNAs in solid tumors. However, DNA extracted from FFPE tumor tissue produces an essential, yet problematic, sample type. The College of American Pathologists/American Society of Clinical Oncology guidelines for optimal tumor tissue handling, published in 2007 for breast cancer and in 2016 for gastroesophageal adenocarcinomas, are lacking for other solid tumors. Thus, cold ischemia times are seldom monitored in non-breast cancer and non-gastroesophageal adenocarcinomas, and all tumor biospecimens are affected by chemical fixation. Although intended to preserve specimens for long-term storage, formalin fixation causes loss of genetic information through DNA damage. Herein, we describe a reference size matching, whole-genome amplification, and fluorescent labeling method for FFPE-derived DNA designed to improve chromosomal microarray results from suboptimal nucleic acids and salvage highly degraded samples. With this technological advance, whole-genome copy number analysis of tumor DNA can be reliably performed in the clinical laboratory for a wide variety of tissue conditions and tumor types.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Genoma Humano
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Cromossomos Humanos
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Fixação de Tecidos
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Inclusão em Parafina
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Análise em Microsséries
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Variações do Número de Cópias de DNA
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Corantes Fluorescentes
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Neoplasias
Tipo de estudo:
Guideline
Limite:
Humans
Idioma:
En
Revista:
J Mol Diagn
Ano de publicação:
2018
Tipo de documento:
Article