Patterns of CTCF and ZFHX3 Mutation and Associated Outcomes in Endometrial Cancer

Journal of the National Cancer Institute
Christopher J WalkerP J Goodfellow

Abstract

The genetic events responsible for tumor aggressiveness in endometrioid endometrial cancer (EEC) remain poorly understood. The chromosome 16q22 tumor suppressor genes CTCF and ZFHX3 are both frequently mutated in EEC, but their respective roles in outcome have not been determined. Targeted deep sequencing of CTCF and ZFHX3 was performed for 542 EEC samples. Copy number loss (CNL) was determined using microsatellite typing of paired tumor and normal DNA and a novel Bayesian method based on variant allele frequencies of germline polymorphisms. All statistical tests were two-sided. Mutation rates for CTCF and ZFHX3 were 25.3% and 20.4%, respectively, and there was a statistically significant excess of tumors with mutation in both genes (P = .003). CNL rates were 17.4% for CTCF and 17.2% for ZFHX3, and the majority of CNLs included both CTCF and ZFHX3. Mutations were more frequent in tumors with microsatellite instability, and CNLs were more common in microsatellite-stable tumors (P < .001). Patients with ZFHX3 mutation and/or CNL had higher-grade tumors (P = .001), were older (P < .001), and tended to have more frequent lymphovascular space invasion (P = .07). These patients had reduced recurrence-free and overall survival (RFS: h...Continue Reading

References

Apr 1, 1971·Proceedings of the National Academy of Sciences of the United States of America·A G Knudson
Feb 1, 1983·Gynecologic Oncology·J V Bokhman
Jul 1, 1995·Obstetrics and Gynecology·M F KohlerA Berchuck
May 13, 1999·The Journal of Biological Chemistry·P KasparM Dvorák
Jun 9, 1999·British Journal of Cancer·Z PiaoH Kim
Jan 28, 2003·Cancer Genetics and Cytogenetics·Lise Lotte HansenIordanis I Arzimanoglou
Jan 13, 2004·Biochemical and Biophysical Research Communications·Shunsuke NojiriMakoto Ito
Nov 6, 2004·Disease Markers·Jeffery W BacherStephen N Thibodeau
Mar 7, 2006·Genes, Chromosomes & Cancer·Emad A RakhaIan O Ellis
Aug 26, 2006·Journal of Cancer Research and Clinical Oncology·Xiaodong SunJin-Tang Dong
May 22, 2007·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Israel ZighelboimDavid G Mutch
Jan 17, 2008·Current Opinion in Obstetrics & Gynecology·Chad A HamiltonJohn K Chan
Feb 1, 2008·Nature·Kerstin S WendtJan-Michael Peters
Feb 2, 2008·Cell·Vania ParelhoMatthias Merkenschlager
Apr 23, 2008·Current Protocols in Human Genetics·S A ForbesM R Stratton
Jun 14, 2008·Proceedings of the National Academy of Sciences of the United States of America·Eric D RubioAnton Krumm
Apr 16, 2009·International Journal of Gynaecology and Obstetrics : the Official Organ of the International Federation of Gynaecology and Obstetrics·Sergio Pecorelli
Apr 5, 2011·American Journal of Human Genetics·Abel González-Pérez, Nuria López-Bigas
May 26, 2012·Science·Nicole L SoliminiStephen J Elledge
May 31, 2012·Genesis : the Journal of Genetics and Development·Xiaodong SunJin-Tang Dong
Nov 7, 2012·Gynecologic Oncology·Akiva P NovetskyPaul J Goodfellow
May 3, 2013·Nature·Cyriac KandothDouglas A Levine
May 11, 2013·Journal of Obstetrics and Gynaecology Canada : JOGC = Journal D'obstétrique Et Gynécologie Du Canada : JOGC·Rachel KupetsUNKNOWN SPECIAL CONTRIBUTORS
Sep 28, 2013·Nature Genetics·UNKNOWN Cancer Genome Atlas Research NetworkJoshua M Stuart
Oct 17, 2013·Human Mutation·Israel ZighelboimPaul J Goodfellow
Oct 31, 2013·Clinical Chemistry·Matthieu Le Gallo, Daphne W Bell
Jan 9, 2014·CA: a Cancer Journal for Clinicians·Rebecca SiegelAhmedin Jemal
May 6, 2014·Cell Reports·Christopher J KempGalina N Filippova

❮ Previous
Next ❯

Citations

Feb 9, 2016·Current Opinion in Genetics & Development·M Ryan Corces, Victor G Corces
Mar 10, 2016·Gynecologic Oncology·Floor J BackesAdrian A Suarez
Apr 18, 2016·Biochimica Et Biophysica Acta·Anna KazanetsMichael Witcher
Jul 28, 2016·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Ming ShanGuoqiang Zhang
Mar 21, 2017·Oncogene·A D MarshallJ E J Rasko
Nov 21, 2017·Journal of the National Cancer Institute·Christopher J WalkerPaul J Goodfellow
May 31, 2018·Molecular Medicine Reports·Jiubai GuoBin Zhu
Oct 2, 2019·International Journal of Molecular Medicine·Mikael Kronborg ChristophersenEstrid Høgdall
Jun 24, 2020·Journal of Cancer Research and Clinical Oncology·Xiaoyun ZhouYushang Cui
Nov 17, 2020·Nucleic Acids Research·Peiwei ChaiXianqun Fan
Apr 4, 2021·Cancers·Adrián Mosquera OrgueiraJosé Luis Bello López
Aug 28, 2021·Cancers·Carini Picardi Morais de CastroSergi Cuartero

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.