In:
PLOS ONE, Public Library of Science (PLoS), Vol. 15, No. 12 ( 2020-12-30), p. e0244558-
Abstract:
DACH1 is a transcriptional repressor and tumor suppressor gene frequently mutated in melanoma, bladder, and prostate cancer. Loss of DACH1 expression is associated with poor prognostic features and reduced overall survival in uterine cancer. In this study, we utilized the Oncology Research Information Exchange Network (ORIEN) Avatar database to determine the frequency of DACH1 mutations in patients with endometrial cancer in our Kentucky population. Methods We obtained clinical and genomic data for 65 patients with endometrial cancer from the Markey Cancer Center (MCC). We examined the clinical attributes of the cancers by DACH1 status by comparing whole-exome sequencing (WES), RNA Sequencing (RNASeq), microsatellite instability (MSI), and tumor mutational burden (TMB). Results Kentucky women with endometrial cancer had an increased frequency of DACH1 mutations (12/65 patients, 18.5%) compared to The Cancer Genome Atlas (TCGA) endometrial cancer population (25/586 patients, 3.8%) with p-value = 1.04E-05. DACH1 mutations were associated with increased tumor mutation count in both TCGA (median 65 vs. 8972, p-value = 7.35E-09) and our Kentucky population (490 vs. 2160, p-value = 6.0E-04). DACH1 mutated patients have a higher tumor mutation burden compared to DACH1 wild-type (24 vs. 6.02, p-value = 4.29E-05). DACH1 mutations showed significant gene co-occurrence patterns with POLE , MLH1 , and PMS2 . DACH1 mutations were not associated with an increase in microsatellite instability at MCC (MSI-H) (p-value = 0.1342). Conclusions DACH1 mutations are prevalent in Kentucky patients with endometrial cancer. These mutations are associated with high tumor mutational burden and co-occur with genome destabilizing gene mutations. These findings suggest DACH1 may be a candidate biomarker for future trials with immunotherapy, particularly in endometrial cancers.
Type of Medium:
Online Resource
ISSN:
1932-6203
DOI:
10.1371/journal.pone.0244558
DOI:
10.1371/journal.pone.0244558.g001
DOI:
10.1371/journal.pone.0244558.g002
DOI:
10.1371/journal.pone.0244558.g003
DOI:
10.1371/journal.pone.0244558.g004
DOI:
10.1371/journal.pone.0244558.g005
DOI:
10.1371/journal.pone.0244558.g006
DOI:
10.1371/journal.pone.0244558.g007
DOI:
10.1371/journal.pone.0244558.g008
DOI:
10.1371/journal.pone.0244558.t001
DOI:
10.1371/journal.pone.0244558.t002
DOI:
10.1371/journal.pone.0244558.t003
DOI:
10.1371/journal.pone.0244558.t004
DOI:
10.1371/journal.pone.0244558.t005
DOI:
10.1371/journal.pone.0244558.t006
DOI:
10.1371/journal.pone.0244558.t007
DOI:
10.1371/journal.pone.0244558.t008
DOI:
10.1371/journal.pone.0244558.s001
DOI:
10.1371/journal.pone.0244558.s002
DOI:
10.1371/journal.pone.0244558.r001
DOI:
10.1371/journal.pone.0244558.r002
DOI:
10.1371/journal.pone.0244558.r003
DOI:
10.1371/journal.pone.0244558.r004
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2020
detail.hit.zdb_id:
2267670-3
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