Integrated data analysis reveals uterine leiomyoma subtypes with distinct driver pathways and biomarkers

Proceedings of the National Academy of Sciences of the United States of America
Miika MehineLauri A Aaltonen

Abstract

Uterine leiomyomas are common benign smooth muscle tumors that impose a major burden on women's health. Recent sequencing studies have revealed recurrent and mutually exclusive mutations in leiomyomas, suggesting the involvement of molecularly distinct pathways. In this study, we explored transcriptional differences among leiomyomas harboring different genetic drivers, including high mobility group AT-hook 2 (HMGA2) rearrangements, mediator complex subunit 12 (MED12) mutations, biallelic inactivation of fumarate hydratase (FH), and collagen, type IV, alpha 5 and collagen, type IV, alpha 6 (COL4A5-COL4A6) deletions. We also explored the transcriptional consequences of 7q22, 22q, and 1p deletions, aiming to identify possible target genes. We investigated 94 leiomyomas and 60 corresponding myometrial tissues using exon arrays, whole genome sequencing, and SNP arrays. This integrative approach revealed subtype-specific expression changes in key driver pathways, including Wnt/β-catenin, Prolactin, and insulin-like growth factor (IGF)1 signaling. Leiomyomas with HMGA2 aberrations displayed highly significant up-regulation of the proto-oncogene pleomorphic adenoma gene 1 (PLAG1), suggesting that HMGA2 promotes tumorigenesis through PL...Continue Reading

References

Aug 1, 1991·Cancer Genetics and Cytogenetics·N PandisF Mitelman
Jun 2, 1998·Nature·S HinumaM Fujino
Oct 26, 1999·The Journal of Biological Chemistry·B H QuD LeRoith
Nov 30, 2000·Biochemical and Biophysical Research Communications·F LoechelU M Wewer
Feb 15, 2001·International Journal of Cancer. Journal International Du Cancer·P J NevilleI G Campbell
Jul 20, 2002·Trends in Endocrinology and Metabolism : TEM·Nira Ben-JonathanMichael Zinger
Dec 30, 2003·Genes, Chromosomes & Cancer·Andrea ZatkovaKatharina Wimmer
Jan 9, 2004·Oncogene·Marianne L VozWim J M Van de Ven
Jun 9, 2005·Oncogene·Sakari VanharantaLauri A Aaltonen
Dec 2, 2005·Human Molecular Genetics·Sakari VanharantaLauri A Aaltonen
Apr 26, 2006·American Journal of Obstetrics and Gynecology·Phyllis C LeppertJames H Segars
Dec 16, 2006·Genes, Chromosomes & Cancer·Lurdes QueimadoAntonio M C Reis
Mar 3, 2007·International Journal of Oncology·Frederik Van DyckWim J M Van de Ven
Jan 19, 2008·International Journal of Oncology·Isabelle Cleynen, Wim J M Van de Ven
Mar 18, 2009·Bioinformatics·Cole TrapnellSteven L Salzberg
Jul 16, 2009·Cancer Genetics and Cytogenetics·Anke van RijkEric F P M Schoenmakers
Dec 16, 2010·Cancer Genetics and Cytogenetics·Maliheh Hashemi NezhadJörn Bullerdiek
Jan 10, 2012·International Journal of Cancer. Journal International Du Cancer·Dominique Nadine MarkowskiJörn Bullerdiek
May 17, 2012·Journal of Midwifery & Women's Health·Kate E RiceJeremy L Neal
Jul 7, 2012·PloS One·Gaëlle PérotFrédéric Chibon
Jul 14, 2012·Cancer Cell·Yoichiro MitsuishiHozumi Motohashi
Jul 20, 2012·Nature Reviews. Cancer·Michael B Sporn, Karen T Liby
Sep 12, 2012·Genes, Chromosomes & Cancer·Eric F P M SchoenmakersAd Geurts van Kessel
Oct 2, 2012·International Journal of Oncology·Monira AkhtarTomas J Ekström
Jan 4, 2013·Proceedings of the National Academy of Sciences of the United States of America·Binny V VargheseVargheese M Chennathukuzhi
Mar 16, 2013·International Journal of Laboratory Hematology·N SavageJ Gotlib
May 15, 2013·Reproductive Biomedicine Online·Dong Zhao, Peter A W Rogers
Jun 7, 2013·The New England Journal of Medicine·Miika MehineLauri A Aaltonen

❮ Previous
Next ❯

Citations

May 18, 2016·British Journal of Cancer·Kati KämpjärviPia Vahteristo
Mar 16, 2017·BJOG : an International Journal of Obstetrics and Gynaecology·E A StewartR Schulze-Rath
Mar 1, 2018·Expert Opinion on Emerging Drugs·Jacques DonnezMarie-Madeleine Dolmans
Sep 21, 2017·International Journal of Molecular Sciences·Veronica SaraisPaola Vigano'
Feb 15, 2018·The Journal of Biological Chemistry·Min Ju ParkThomas G Boyer
Apr 28, 2018·Endocrine-related Cancer·Vanida A SernaTakeshi Kurita
Apr 17, 2018·Cancer Science·Hideaki Tsuyoshi, Yoshio Yoshida
Oct 27, 2017·Reproduction : the Official Journal of the Society for the Study of Fertility·Yi-An KoPradeep S Tanwar
Jan 22, 2018·Journal of Gastroenterology·Patricia Sanmartín-SalinasLuis Gonzalez Guijarro
Sep 2, 2017·International Journal of Gynecological Pathology : Official Journal of the International Society of Gynecological Pathologists·Qing ZhangJian-Jun Wei
Sep 3, 2017·Archives of Gynecology and Obstetrics·Luz Angela Torres-de la RocheRudy Leon De Wilde
Aug 22, 2018·Obstetrics and Gynecology·Shannon K Laughlin-Tommaso, Elizabeth A Stewart
Jul 13, 2018·The American Journal of Surgical Pathology·Jennifer A BennettEsther Oliva
Sep 6, 2018·Biology of Reproduction·Aymara Mas, Carlos Simón
Nov 30, 2018·The American Journal of Surgical Pathology·Javier A Arias-StellaSarah Chiang
May 23, 2018·Endocrinology·M Fairuz B JamaluddinPradeep S Tanwar
Oct 27, 2017·British Journal of Cancer·Hanna-Riikka HeinonenEevi Kaasinen
Sep 7, 2017·Archives of Gynecology and Obstetrics·Antonio Simone LaganàSalvatore Giovanni Vitale
Aug 14, 2018·The Journal of Clinical Endocrinology and Metabolism·Min Ju ParkThomas G Boyer
Nov 21, 2019·Journal of Clinical Laboratory Analysis·Elnaz FazeliReza Mirfakhraie
Apr 30, 2019·Current Opinion in Oncology·Frédéric ChibonGaëlle Pérot
Jun 8, 2017·Oncotarget·Ioannis PanagopoulosSverre Heim
Jun 28, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Binya LiuQin Yan
Aug 3, 2020·Current Opinion in Obstetrics & Gynecology·Esra CetinMichał Ciebiera
Apr 23, 2017·Scientific Reports·Hanna-Riikka HeinonenLauri A Aaltonen
Sep 13, 2018·Laboratory Investigation; a Journal of Technical Methods and Pathology·Jia XieJian-Jun Wei
Feb 23, 2019·JCO Precision Oncology·Matthew L HemmingBrian D Crompton
Aug 8, 2019·International Journal of Molecular Sciences·Dana DvorskáZuzana Danková
Nov 16, 2019·Journal of Assisted Reproduction and Genetics·Shun SatoNorihiro Sugino
Jul 3, 2020·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Bernt PoppAbbas Agaimy
Dec 11, 2019·International Journal of Molecular Sciences·Vladislav S BaranovMaria I Yarmolinskaya
Apr 30, 2020·International Journal of Molecular Sciences·Michał CiebieraArtur Czekierdowski
Dec 1, 2017·Journal of Molecular Histology·Patricia Sanmartín-SalinasLuis G Guijarro
May 8, 2018·Reproductive Sciences·M Fairuz B JamaluddinPradeep S Tanwar
Feb 6, 2020·Reproductive Sciences·Minnie MalikWilliam H Catherino
Apr 17, 2019·Molecular Biology Reports·Angela T Alleyne, Virgil S Bideau
Jan 29, 2020·Current Pharmaceutical Design·Andrea TinelliDaniele Vergara
Apr 29, 2020·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Zehra OrduluNatalia Buza

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cadherins and Catenins

Cadherins (named for "calcium-dependent adhesion") are a type of cell adhesion molecule (CAM) that is important in the formation of adherens junctions to bind cells with each other. Catenins are a family of proteins found in complexes with cadherin cell adhesion molecules of animal cells: alpha-catenin can bind to β-catenin and can also bind actin. β-catenin binds the cytoplasmic domain of some cadherins. Discover the latest research on cadherins and catenins here.

Adherens Junctions

An adherens junction is defined as a cell junction whose cytoplasmic face is linked to the actin cytoskeleton. They can appear as bands encircling the cell (zonula adherens) or as spots of attachment to the extracellular matrix (adhesion plaques). Adherens junctions uniquely disassemble in uterine epithelial cells to allow the blastocyst to penetrate between epithelial cells. Discover the latest research on adherens junctions here.

Related Papers

European Journal of Human Genetics : EJHG
Netta MäkinenLauri A Aaltonen
European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)
Sabrina Croce, Frédéric Chibon
© 2022 Meta ULC. All rights reserved