Molecular subtypes of uterine leiomyosarcoma and correlation with clinical outcome

Neoplasia : an International Journal for Oncology Research
Joyce N BarlinDouglas A Levine

Abstract

The molecular etiology of uterine leiomyosarcoma (ULMS) is poorly understood, which accounts for the wide disparity in outcomes among women with this disease. We examined and compared the molecular profiles of ULMS and normal myometrium (NL) to identify clinically relevant molecular subtypes. Discovery cases included 29 NL and 23 ULMS specimens. RNA was hybridized to Affymetrix U133A 2.0 transcription microarrays. Differentially expressed genes and pathways were identified using standard methods. Fourteen NL and 44 ULMS independent archival samples were used for external validation. Molecular subgroups were correlated with clinical outcome. Pathway analyses of differentially expressed genes between ULMS and NL samples identified overrepresentation of cell cycle regulation, DNA repair, and genomic integrity. External validation confirmed differential expression in 31 genes (P < 4.4 × 10(-4), Bonferroni corrected), with 84% of the overexpressed genes, including CDC7, CDC20, GTSE1, CCNA2, CCNB1, and CCNB2, participating in cell cycle regulation. Unsupervised clustering of ULMS identified two clades that were reproducibly associated with progression-free (median, 4.0 vs 26.0 months; P = .02; HR, 0.33) and overall (median, 18.2 vs 7...Continue Reading

References

Dec 1, 1986·International Journal of Radiation Oncology, Biology, Physics·N B HornbackF J Major
Feb 13, 2003·Nucleic Acids Research·Rafael A IrizarryTerence P Speed
Apr 16, 2003·Gynecologic Oncology·Donald G GallupUNKNOWN Gynecologic Oncology Group Study
Jul 29, 2003·Proceedings of the National Academy of Sciences of the United States of America·John D Storey, Robert Tibshirani
Aug 28, 2003·Cancer·Keith M Skubitz, Amy P N Skubitz
Oct 4, 2005·Proceedings of the National Academy of Sciences of the United States of America·Aravind SubramanianJill P Mesirov
Nov 18, 2005·Gynecologic Oncology·Aliza L LeiserRobert A Soslow
May 2, 2006·Statistical Applications in Genetics and Molecular Biology·Gordon K Smyth
Feb 19, 2008·Nature Biotechnology·Gary K GeissKrassen Dimitrov
Mar 4, 2009·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Oliver ZivanovicMartee L Hensley
Jun 19, 2010·The American Journal of Pathology·Laura S DanielsonEva Hernando
Apr 27, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Weiwei ShanMatthew L Anderson

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Citations

Oct 11, 2016·Sarcoma·Heather MillerMatthew L Anderson
Oct 19, 2016·Expert Review of Anticancer Therapy·Birgit RommelJörn Bullerdiek
Dec 18, 2016·The Journal of Obstetrics and Gynaecology Research·Liping XiaDewei Wang
Mar 25, 2017·Expert Review of Molecular Diagnostics·Ben Davidson, Francesca Micci
Jul 8, 2018·International Journal of Cancer. Journal International Du Cancer·Giorgia SimonettiGiovanni Martinelli
Sep 6, 2018·Biology of Reproduction·Aymara Mas, Carlos Simón
Dec 14, 2018·The Oncologist·Nathan D SeligsonJames L Chen
Apr 21, 2017·Oncotarget·Javier Pérez-PeñaAlberto Ocaña
Nov 13, 2015·Expert Review of Anticancer Therapy·Jennifer A Ducie, Mario M Leitao
Jun 3, 2017·Scientific Reports·Kyle M SchachtschneiderLawrence B Schook
Oct 25, 2017·International Journal of Cancer. Journal International Du Cancer·Tine CuppensFrédéric Amant
Feb 5, 2021·Gynecologic Oncology Reports·Yannan J WangBunja Rungruang

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Datasets Mentioned

BETA
GSE64763

Methods Mentioned

BETA
surgical resection
hysterectomy

Clinical Trials Mentioned

NCT01533207

Software Mentioned

NanoString nCounter
nCounter
NanoString
nCounter Digital Analyzer
GSEA

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