Elsevier

New Biotechnology

Volume 55, 25 March 2020, Pages 30-35
New Biotechnology

Review Article
Pre-analytics and tumor heterogeneity

https://doi.org/10.1016/j.nbt.2019.09.007Get rights and content
Under a Creative Commons license
open access

Highlights

  • Inappropriate pre-analytical conditions can generate false tumor heterogeneities.

  • A new type of tumor sampling is highly recommended for intra-tumor heterogeneity analyses.

  • Only standardized procedures should be allowed in bio-specimen processing.

  • In the past, standardization of pre-analytics was not applied.

Abstract

When dealing with pre-analytics for tissues, it is often that case that tissue heterogeneity, and particularly tumor heterogeneity, is not taken into account as a preliminary condition for obtaining reproducible results in molecular analysis at the diagnostics and clinical research levels. It is well known that when sampling tumor tissues in different areas, for example the border or the central area of the tumor, different genes are expressed and, due to polyclonality in most tumors, different areas can have different DNA and epigenetic alterations. For this reason, it is extremely important to establish and standardize specific tissue sampling protocols for molecular extraction as well as in situ molecular methods. A correct approach to heterogeneity is the basis for a more reproducible and exchangeable type of molecular analysis that can provide useful information at the prognostic and predictive levels. Heterogeneity should also be taken into consideration during cancer treatment, since therapy modifies the clonal composition of tumors. Here, the different types of tumor heterogeneity and the improper pre-analytical conditions in tissue processing that can generate heterogeneous artefacts are described.

Abbreviations

CNNA
copy number alterations
EMT
epithelial-mesenchymal transition
FFPE
formalin-fixed and paraffin-embedded
IHC
immunohistochemistry
ISH
in situ hybridization
ITH
intra-tumor heterogeneity
NGS
next generation sequencing
RNA-seq
RNA-sequencing
SNV
single nucleotide variants
UNG
uracil N-glycosylase

Keywords

Heterogeneity
Intra-tumor heterogeneity
Pre-analytics
Standardized sampling
Molecular diagnostics
Clinical research

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