Landscape of chromatin remodeling gene alterations in endometrial carcinoma Journal Article


Authors: Momeni-Boroujeni, A.; Vanderbilt, C.; Yousefi, E.; Abu-Rustum, N. R.; Aghajanian, C.; Soslow, R. A.; Ellenson, L. H.; Weigelt, B.; Murali, R.
Article Title: Landscape of chromatin remodeling gene alterations in endometrial carcinoma
Abstract: Objective: Chromatin remodeling genes (CRGs) encode components of epigenetic regulatory mechanisms and alterations in these genes have been identified in several tumor types, including gynecologic cancers. In this study, we sought to investigate the prevalence and clinicopathological associations of CRG alterations in endometrial carcinoma (EC). Methods: We performed a retrospective analysis of 660 ECs sequenced using a clinical massively parallel sequencing assay targeting up to 468 genes, including 25 CRGs, and defined the presence of somatic CRG alterations. Clinicopathologic features were obtained for all cases. Immunohistochemical interrogation of ARID1A and PTEN proteins was performed in a subset of samples. Results: Of the 660 ECs sequenced, 438 (66.4%) harbored CRG alterations covered by our panel. The most commonly altered CRG was ARID1A (46%), followed by CTCF (21%), KMT2D (18%), KMT2B (17%), BCOR (16%), ARID1B (12%) and SMARCA4 (11%). We found that ARID1A genetic alterations were preferentially bi-allelic and often corresponded to altered ARID1A protein expression in ECs. We further observed that ARID1A alterations were often subclonal when compared to PTEN alterations, which were primarily clonal in ECs harboring both mutations. Finally, CRG alterations were associated with an increased likelihood of myometrial and lymphovascular invasion in endometrioid ECs. Conclusion: CRG alterations are common in EC and are associated with clinicopathologic features and likely play a crucial role in EC. © 2023 Elsevier Inc.
Keywords: genetics; transcriptomics; mutations; massively parallel sequencing; chromatin remodeling; dna, endometrial carcinoma; rna, swi/snf
Journal Title: Gynecologic Oncology
Volume: 172
ISSN: 0090-8258
Publisher: Elsevier Inc.  
Date Published: 2023-05-01
Start Page: 54
End Page: 64
Language: English
DOI: 10.1016/j.ygyno.2023.03.010
PROVIDER: scopus
PUBMED: 36958196
PMCID: PMC10192087
DOI/URL:
Notes: The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PDF -- Corresponding author is MSK author: Rajmohan Murali -- Source: Scopus
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MSK Authors
  1. Robert Soslow
    797 Soslow
  2. Rajmohan Murali
    220 Murali
  3. Britta Weigelt
    643 Weigelt
  4. Lora Hedrick Ellenson
    111 Ellenson