Frequent POLE1 p.S297F mutation in Chinese patients with ovarian endometrioid carcinoma

Zou, Yang; Liu, Faying; Liu, Huai; Wang, Feng; Li, Wei; Huang, Meizhen; Huang, Yan; Yuan, Xiao-Qun; Xu, Xiaoyun; Huang, Ouping; He, Ming

doi:10.1016/j.mrfmmm.2014.01.003

Cited by 29 publications

(30 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Among these patients, the POLE1 mutation has been previously found to be frequent in 37 ovarian endometrioid carcinomas (26), whereas ring finger protein 43 (RNF43) mutations were recurrent in 15 mucinous ovarian carcinomas (25) ( Table I). In the present study, neither endometrioid nor mucinous ovarian carcinomas were detected to harbor DICER1, CTCF, RPL22, DNMT3A, TRRAP, IDH1 and IDH2 hotspot mutations.…”

Section: Resultsmentioning

confidence: 99%

“…The available clinical data of these patients are as described previously (25,26). In the present study, a total of 251 Chinese samples with distinct subtypes of ovarian carcinoma were screened for the presence of potential hotspot mutations in the DICER1, CTCF, RPL22, DNMT3A, TRRAP, IDH1 and IDH2 genes.…”

Section: Resultsmentioning

confidence: 99%

“…Considering the fact that ovarian carcinoma have certain overlapped genetic aberrations with endometrial cancer, such as frequent TP53 (9,30) and polymerase (DNA directed) ε, catalytic subunit (POLE1) mutations (26,30), we hypothesized that ovarian carcinomas may also harbor these mutations. However, neither CTCF p.T204fs* nor RPL22 c.43delA mutations were identified in the samples in the present study.…”

Section: Resultsmentioning

confidence: 99%

“…Only those patients with >70% of neoplastic cells were recruited in the study. The sample cohort contained 76 ovarian serous carcinoma, 43 ovarian clear cell carcinoma, 37 ovarian endometrioid carcinoma, 33 ovarian germ cell tumor, 15 mucinous ovarian carcinoma, 18 ovarian sex cord-stromal tumor, 12 other rare subtypes and 17 Krukenberg tumor, and the available clinical data was as described previously (25,26) and in Table I. Informed consent conforming to the tenets of the Declaration of Helsinki was obtained from each patient prior to the study.…”

Section: Methodsmentioning

confidence: 99%

“…PCR reactions were performed in a total volume of 25 µl, containing 50 ng genomic DNA, 2 units of LA Taq DNA Polymerase (Takara Biotechnology Dalian Co. Ltd., Liaoning, China), 300 µM of each dNTP and 0.2 µM of each primer. The amplification reaction was performed in a Thermal Cycler 2720 (Applied Biosystems, Foster City, CA, USA) and employed one denaturation cycle of 94˚C for 3 min, 35 amplification cycles of 94˚C for 30 sec, 50-60˚C (Table II) As per references (25,26); POLE1, polymerase (DNA directed) ε, catalytic subunit; RNF43, ring finger protein 43.…”

Section: Methodsmentioning

confidence: 99%

See 4 more Smart Citations

Absence of DICER1, CTCF, RPL22, DNMT3A, TRRAP, IDH1 and IDH2 hotspot mutations in patients with various subtypes of ovarian carcinomas

et al. 2014

Self Cite

View full text Add to dashboard Cite

Abstract.Cancer is caused by multiple genetic alterations within cells. Recently, large-scale sequencing has identified frequent ribonuclease type III (DICER1), CCCTC-binding factor (CTCF), ribosomal protein L22 (RPL22), DNA (cytosine-5-)-methyltransferase 3α (DNMT3A), transformation/transcription domain-associated protein (TRRAP), isocitrate dehydrogenase (IDH)1 and IDH2 hotspot mutations in diverse types of cancer. However, it remains largely unknown whether these mutations also exist in ovarian carcinomas. In the present study, a collection of 251 patients with distinct subtypes of ovarian carcinomas were recruited and sequenced for the presence of these hotspot mutations. However, no mutations in the seven genes were detected in the samples. These negative results, together with certain recent reports, indicate that the hotspot mutations in the CTCF, RPL22, DNMT3A, TRRAP, IDH1 and IDH2 genes may not be actively involved in the carcinogenesis of ovarian carcinoma. Of note, the DICER1 mutation frequency in Sertoli-Leydig cell tumor in the present study was significantly lower compared to prior observation, and therefore, it is speculated that this discrepancy may be mainly due to the small sample size analyzed in the study. In addition, among these samples, frequent polymerase (DNA directed) ε, catalytic subunit (POLE1) and ring finger protein 43 (RNF43) mutations were identified in endometrioid and mucinous ovarian carcinomas, respectively; thus DICER1, CTCF, RPL22, DNMT3A, TRRAP, IDH1 and IDH2 hotspot mutations may not play synergistic roles with POLE1 or RNF43 mutations in the carcinogenesis of endometrioid or mucinous ovarian carcinomas. IntroductionThe current understanding of human malignancy is that it mainly arises due to the accumulation of multiple genetic alterations, transforming normal cells into malignant cells (1,2). Of these genetic alterations, a myriad of genomic mutation data derived from a high-throughput DNA sequencing technique provided a unique opportunity to profile the mutation spectra underlying human cancers and a large number of significant functional mutations in multiple genes were identified in diverse types of cancer (1,3,4). These genes can be defined as oncogenes or tumor suppressor genes and are being used as molecular markers for diagnosis, staging and prognosis of human cancers (5,6).Ovarian carcinoma constitutes a heterogeneous group of malignancies with significantly different clinical expression, pathological characteristics and genetic etiology (7,8). However, the majority of ovarian carcinomas shared certain common genetic alterations, such as frequent tumor protein p53 (TP53) and PIK3CA, catalytic subunit α mutations (9,10), and patients also exhibited subtype-specific mutations (11-13), which are possibly essential for the differential clinical expression and molecular-targeted therapy in ovarian carcinomas (14,15). These observations emphasized the requirement to identify novel subtype-specific molecular genetic aberrations in ovarian carcinomas.Recently, large-scal...

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 3 more Smart Citations

Absence of DICER1, CTCF, RPL22, DNMT3A, TRRAP, IDH1 and IDH2 hotspot mutations in patients with various subtypes of ovarian carcinomas

et al. 2014

Self Cite

View full text Add to dashboard Cite

show abstract

Constitutional POLE variants causing a phenotype reminiscent of constitutional mismatch repair deficiency

et al. 2021

View full text Add to dashboard Cite

Heterozygous POLE or POLD1 germline pathogenic variants (PVs) cause polymerase proofreading associated polyposis (PPAP), a constitutional polymerase proofreading deficiency that typically presents with colorectal adenomas and carcinomas in adulthood. Constitutional mismatch‐repair deficiency (CMMRD), caused by germline bi‐allelic PVs affecting one of four MMR genes, results in a high propensity for the hematological, brain, intestinal tract, and other malignancies in childhood. Nonmalignant clinical features, such as skin pigmentation alterations, are found in nearly all CMMRD patients and are important diagnostic markers. Here, we excluded CMMRD in three cancer patients with highly suspect clinical phenotypes but identified in each a constitutional heterozygous POLE PV. These, and two additional POLE PVs identified in published CMMRD‐like patients, have not previously been reported as germline PVs despite all being well‐known somatic mutations in hyper‐mutated tumors. Together, these five cases show that specific POLE PVs may have a stronger “mutator” effect than known PPAP‐associated POLE PVs and may cause a CMMRD‐like phenotype distinct from PPAP. The common underlying mechanism, that is, a constitutional replication error repair defect, and a similar tumor spectrum provide a good rationale for monitoring these patients with a severe constitutional polymerase proofreading deficiency according to protocols proposed for CMMRD.

show abstract

Adenomatous Polyposis Syndromes: Polymerase Proofreading-Associated Polyposis

Palles

Latchford

Valle

2018

Hereditary Colorectal Cancer

View full text Add to dashboard Cite

Frequent POLE1 p.S297F mutation in Chinese patients with ovarian endometrioid carcinoma

Cited by 29 publications

References 21 publications

Absence of DICER1, CTCF, RPL22, DNMT3A, TRRAP, IDH1 and IDH2 hotspot mutations in patients with various subtypes of ovarian carcinomas

Absence of DICER1, CTCF, RPL22, DNMT3A, TRRAP, IDH1 and IDH2 hotspot mutations in patients with various subtypes of ovarian carcinomas

Constitutional POLE variants causing a phenotype reminiscent of constitutional mismatch repair deficiency

Adenomatous Polyposis Syndromes: Polymerase Proofreading-Associated Polyposis

Contact Info

Product

Resources

About