NDLI: Regional Bias of Intratumoral Genetic Heterogeneity of Nucleotide Repeats in Colon Cancers with Microsatellite Instability

Content Provider	Springer Nature Link
Author	Choi, Youn Jin Kim, Min Sung An, Chang Hyeok Yoo, Nam Jin Lee, Sug Hyung
Copyright Year	2014
Abstract	Intratumoral heterogeneity (ITH) may produce regional biases in genotype and phenotype evaluation in a single tumor and may impede proper cancer diagnosis. To evaluate the extent of ITH in colorectal cancer (CRC) with microsatellite instability (MSI), we obtained 4–7 biopsies from 39 CRCs followed by MSI analysis either using the Bethesda MSI evaluation system or Promega system with 5 mononucleotide markers. We found decreased prevalence of MSI (+) by the Promega system compared to the Bethesda system. The overall discordance between the two systems was 54 %. In contrast to the previous studies that had shown discordance only in low MSI (MSI-L), our results showed the discordance not only in MSI-L, but also in high MSI (MSI-H) cases. Among the MSI (+) CRCs, ITH of MSI status was identified in 41.7 % of CRC by the Bethesda system and 22.2 % by the Promega system. In terms of MSI markers, the ITH originated from dinucleotide markers in most cases (69 %), but it originated from mononucleotide markers (31 %) as well. Pooling of DNA from a regional biopsy with MSI (+) with additional biopsies from stable MSI (MSS) showed that this approach was beneficial to increase the sensitivity of MSI detection. Our results indicate that ITH of MSI phenotype by the Bethesda system is more overestimated than previously identified. However, because there was considerable ITH of MSI subtypes and markers even by the Promega system, our data suggest that analysis of MSI status in multiple regional biopsies is needed for a better evaluation of MSI status in CRC.
Starting Page	965
Ending Page	971
Page Count	7
File Format	PDF
ISSN	12194956
Journal	Pathology & Oncology Research
Volume Number	20
Issue Number	4
e-ISSN	15322807
Language	English
Publisher	Springer Netherlands
Publisher Date	2014-04-21
Publisher Place	Dordrecht
Access Restriction	Subscribed
Subject Keyword	Bethesda panel Colorectal cancer Dinucleotide repeats Intratumoral heterogeneity Microsatellite instability Mononucleotide repeats Promega panel Cancer Research Oncology Pathology Immunology Biomedicine general
Content Type	Text
Resource Type	Article
Subject	Cancer Research Pathology and Forensic Medicine Oncology

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