Molecular subtypes of uterine leiomyosarcoma and correlation with clinical outcome Journal Article

Authors: Barlin, J. N.; Zhou, Q. C.; Leitao, M. M.; Bisogna, M.; Olvera, N.; Shih, K. K.; Jacobsen, A.; Schultz, N.; Tap, W. D.; Hensley, M. L.; Schwartz, G. K.; Boyd, J.; Qin, L. X.; Levine, D. A.
Article Title: Molecular subtypes of uterine leiomyosarcoma and correlation with clinical outcome
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 77.2 months; P =.04; HR, 0.33) survival. Cell cycle genes play a key role in ULMS sarcomagenesis, providing opportunities for therapeutic targeting. Reproducible molecular subtypes associated with clinical outcome may permit individualized adjuvant treatment after clinical trial validation. © 2015 The Authors.
Keywords: adult; cancer survival; controlled study; human tissue; aged; cancer surgery; major clinical study; overall survival; validation process; cancer adjuvant therapy; cancer staging; antineoplastic agent; hysterectomy; dna repair; progression free survival; gene expression; gene expression profiling; rna; dna; microarray analysis; cell cycle regulation; uterus sarcoma; molecular pathology; cladistics; cyclin a2; cell cycle protein 20; rna hybridization; human; female; priority journal; article
Journal Title: NeoPlasia
Volume: 17
Issue: 2
ISSN: 1522-8002
Publisher: Elsevier Science Inc.  
Date Published: 2015-02-01
Start Page: 183
End Page: 189
Language: English
DOI: 10.1016/j.neo.2014.12.007
PROVIDER: scopus
PMCID: PMC4351299
PUBMED: 25748237
Notes: Article -- Export Date: 3 October 2016 -- Source: Scopus
Citation Impact
MSK Authors
  1. Gary Schwartz
    383 Schwartz
  2. Douglas A Levine
    363 Levine
  3. Mario Leitao
    360 Leitao
  4. Joyce Nuqui Barlin
    23 Barlin
  5. Qin Zhou
    140 Zhou
  6. Li-Xuan Qin
    130 Qin
  7. Martee L Hensley
    237 Hensley
  8. Karin Kuan-Hui Shih
    41 Shih
  9. Narciso Olvera
    71 Olvera
  10. William Douglas Tap
    176 Tap
  11. Nikolaus D Schultz
    259 Schultz