ArticleGenome research2012
Whole-exome sequencing combined with functional genomics reveals novel candidate driver cancer genes in endometrial cancer.
Article in Genome research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 153 papers, 1 of them a synthesis that pooled it.
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Who cites it
153 citing papers in PubMed, 1 synthesis or guideline pooled it, 245 citations in OpenAlex.
- Genomic and epigenomic heterogeneity in molecular subtypes of gastric cancer.World journal of gastroenterology · 2016Pooled it
- Phase II, 2-stage, 2-arm, PIK3CA mutation stratified trial of MK-2206 in recurrent endometrial cancer.International journal of cancer · 2020Trial
- Safety lead-in of the MEK inhibitor trametinib in combination with GSK2141795, an AKT inhibitor, in patients with recurrent endometrial cancer: An NRG Oncology/GOG study.Gynecologic oncology · 2019Trial
- Pathogenesis and potential therapeutic targets of trichorhinophalangeal syndrome; lessons obtained from animal studies.Developmental dynamics : an official publication of the American Association of Anatomists · 2026Review
- <p>KMO downregulation promotes hepatocellular carcinoma growth via 3‑HAA‑mediated mitochondrial mass and function imbalances</p>.International journal of oncology · 2026Article
- Wnt/β-catenin activation by mutually exclusive FBXW11 and CTNNB1 hotspot mutations drives salivary basal cell adenoma.Nature communications · 2025Article
- AKT inhibitors in gynecologic oncology: past, present and future.Frontiers in oncology · 2025Review
- Advances in DNA/RNA Sequencing and Their Applications in Acute Myeloid Leukemia (AML).International journal of molecular sciences · 2024Review
- Review
- A protein expression atlas on tissue samples and cell lines from cancer patients provides insights into tumor heterogeneity and dependencies.Nature cancer · 2024Article
- Single-cell exome sequencing reveals polyclonal seeding and TRPS1 mutations in colon cancer metastasis.Signal transduction and targeted therapy · 2024Article
- ARID1A in Gynecologic Precancers and Cancers.Reproductive sciences (Thousand Oaks, Calif.) · 2024Review
- Proteogenomic insights into early-onset endometrioid endometrial carcinoma: predictors for fertility-sparing therapy response.Nature genetics · 2024Article
- Translational Aspects of Epithelioid Sarcoma: Current Consensus.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Review
- Therapeutic Role of Synthetic Lethality inJournal of immunotherapy and precision oncology · 2024Review
- Advances in the study of the role of high-frequency mutant subunits of the SWI/SNF complex in tumors.Frontiers in oncology · 2024Review
- Explore the alterations of downstream molecular pathways caused by ARID1A mutation/knockout in human endometrial cancer cells.Journal of cancer research and clinical oncology · 2023Article
- Impact of ARID1A and TP53 mutations in pediatric refractory or relapsed mature B-Cell lymphoma treated with CAR-T cell therapy.Cancer cell international · 2023Article
- The interplay of obesity, microbiome dynamics, and innovative anti-obesity strategies in the context of endometrial cancer progression and therapeutic approaches.Biochimica et biophysica acta. Reviews on cancer · 2023Review
- TRPS1 regulates the opposite effect of progesterone via RANKL in endometrial carcinoma and breast carcinoma.Cell death discovery · 2023Article
93 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
24 authors at 3 institutions in 1 country.
Funding
Abstract
Endometrial cancer is the most common gynecological malignancy, with more than 280,000 cases occurring annually worldwide. Although previous studies have identified important common somatic mutations in endometrial cancer, they have primarily focused on a small set of known cancer genes and have thus provided a limited view of the molecular basis underlying this disease. Here we have developed an integrated systems-biology approach to identifying novel cancer genes contributing to endometrial tumorigenesis. We first performed whole-exome sequencing on 13 endometrial cancers and matched normal samples, systematically identifying somatic alterations with high precision and sensitivity. We then combined bioinformatics prioritization with high-throughput screening (including both shRNA-mediated knockdown and expression of wild-type and mutant constructs) in a highly sensitive cell viability assay. Our results revealed 12 potential driver cancer genes including 10 tumor-suppressor candidates (ARID1A, INHBA, KMO, TTLL5, GRM8, IGFBP3, AKTIP, PHKA2, TRPS1, and WNT11) and two oncogene candidates (ERBB3 and RPS6KC1). The results in the "sensor" cell line were recapitulated by siRNA-mediated knockdown in endometrial cancer cell lines. Focusing on ARID1A, we integrated mutation profiles with functional proteomics in 222 endometrial cancer samples, demonstrating that ARID1A mutations frequently co-occur with mutations in the phosphatidylinositol 3-kinase (PI3K) pathway and are associated with PI3K pathway activation. siRNA knockdown in endometrial cancer cell lines increased AKT phosphorylation supporting ARID1A as a novel regulator of PI3K pathway activity. Our study presents the first unbiased view of somatic coding mutations in endometrial cancer and provides functional evidence for diverse driver genes and mutations in this disease.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.