WRN -Mutated Colorectal Cancer Is Characterized by a Distinct Genetic Phenotype
Werner syndrome gene ( ) contributes to DNA repair. In cancer, mutations ( -mut) lead to genomic instability. Thus, is a promising target in cancers with microsatellite instability (MSI). We assessed this study to investigate the molecular profile of -mut in colorectal cancer (CRC). Tumor samples we...
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Published in | Cancers Vol. 12; no. 5; p. 1319 |
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Main Authors | , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Switzerland
MDPI AG
22.05.2020
MDPI |
Subjects | |
Online Access | Get full text |
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Summary: | Werner syndrome gene (
) contributes to DNA repair. In cancer,
mutations (
-mut) lead to genomic instability. Thus,
is a promising target in cancers with microsatellite instability (MSI). We assessed this study to investigate the molecular profile of
-mut in colorectal cancer (CRC). Tumor samples were analyzed using next-generation sequencing (NGS) in-situ hybridization and immunohistochemistry. Tumor mutational burden (TMB) was calculated based on somatic nonsynonymous missense mutations. Determination of tumor mismatch repair (MMR) or microsatellite instability (MSI) status was conducted by fragment analysis.
-mut were detected in 80 of 6854 samples (1.2%).
-mut were more prevalent in right-sided compared to left-sided CRC (2.5% vs. 0.7%,
< 0.0001). TMB, PD-L1 and MSI-H/dMMR were significantly higher in
-mut than in
wild-type (WRN-wt). WRN-mut were associated with a higher TMB in the MSI-H/dMMR and in the MSS (microsatellite stable) subgroups. Several genetic differences between
-mut and
-wt CRC were observed, i.e.,
(47% vs. 71%),
(34% vs. 49%) and
(56% vs. 73%). This is the largest molecular profiling study investigating the genetic landscape of
-mut CRCs so far. A high prevalence of MSI-H/dMMR, higher TMB and PD-L1 in
-mut tumors were observed. Our data might serve as an additional selection tool for trials testing immune checkpoint antibodies in
-mut CRC. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 2072-6694 2072-6694 |
DOI: | 10.3390/cancers12051319 |