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Beird, Hannah C

Broaddus, Russell R

Celestino, Joseph

Futreal, Andrew

Gershenson, David M., MD

Gumbs, Curtis

Hillman, R Tyler

Khlebus, Eleonora

Khurana, Namrata

Lawson, Barrett

Little, Latasha

Nguyen, Tri

Vuttaradhi, Veena K

Welte, Thomas

English

OpenWorks @ MD Anderson

• Adult-type granulosa cell tumor (aGCT) is a rare ovarian sex-cord stromal tumor (~ 5% of all ovarian tumors)• Most primary aGCTs are diagnosed at an early stage and can be removed surgically with long-term survival rates exceeding 90%• aGCT recurrence is difficult to predict and is almost always incurable after relapse Eleonora Khlebuseykhlebus@mdanderson.orgGranulosa cells OocyteDifferential Gene Expression analysisCryopreserved tumor tissue samples (n=24)Primary aGCTs(n=8)Recurrent aGCTs(n=16)Bulk RNA-sequencingTumor Microenvironment analysisGene Set Enrichment Analysis (GSEA)vsRanked gene listThe objective:Identify the differences between Primary and Recurrent aGCTs which may correlate with recurrenceDifferentially expressed genesEnriched gene sets Comparative Transcriptomic Analysis of Primary and Recurrent Ovarian Granulosa Cell TumorsEleonora Khlebusa*, Veena K. Vuttaradhia, Thomas Weltea, Namrata Khuranaa, Joseph Celestinob, Hannah C. Beirda, Curtis Gumbsa, Latasha Littlea,Tri Nguyenb, Barrett Lawsonc, Russell R. Broaddusd, David M. Gershensonb, P. Andrew Futreala, and R. Tyler Hillmana,baDepartment of Genomic Medicine, bDepartment of Gynecologic Oncology and Reproductive Medicine, cDepartment of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USAdDepartment of Pathology and Laboratory Medicine, The University of North Carolina, Chapel Hill, NC, 27599, USA*eykhlebus@mdanderson.orgLeading Edge of Cancer Research Symposium 2022 Differential Gene Expression analysis: Recurrent vs Primary tumors• 31 differentially expressed gene identified (Padj < 0.05, FoldChange > 2) • Functional Enrichment analysis: Gene Set Enrichment Higher Expression in Primary Tumors: • LHCGR and INSL3 - genes involved in normal ovarian sex cord hormonal signaling Higher Expression in Recurrent Tumors:• NELL2, GDF6, and IL1RL1 - in some cancer types increases expression of these genes were associated with increased metastasis and decreased survival rate• CYP19A1 (aromatase) expression may be closely linked to aGCT pathogenesis and progressionPrimarily immune-related and hormone-regulated gene sets expression was increased in recurrent tumorsEleonora Khlebuseykhlebus@mdanderson.orgComparative tumor microenvironment analysis § Tumor microenvironment composition is significantly different between primary and recurrent aGCTs• Recurrent tumors have increased myeloid fraction and reduced prevalence of stromal cells what can promote tumor progression§ Expression of genes involved in ovarian hormone signaling was identified as significantly altered in recurrences• Changes in hormonal signaling pathways may underpin aGCT recurrenceModified from Newman et al. (2019) Nat Biotech.• Tumor microenvironment in silico cytometryCIBERSORTx• Tumor microenvironment analysisConclusions:Financial support: This work was supported by grants from the Cancer Prevention and Research Institute of Texas (CPRIT) to R.T.H. (RR200045) and P.A.F. (R1205). R.T.H. is supported by the Jennifer “Jenny” Song Fund for Granulosa Cell Tumor Research. The University of Texas MD Anderson Cancer Center Multidisciplinary Gynecologic Cancer Tumor Bank is supported in part by NIH P50CA83639 SPORE in Ovarian Cancer.The authors declare no potential conflicts of interest.Eleonora Khlebuseykhlebus@mdanderson.orgHigher fractions in Recurrent tumors Lower fractions in Recurrent tumors 

Comparative Transcriptomic Analysis of Primary and Recurrent Ovarian Granulosa Cell Tumors

https://openworks.mdanderson.org/cgi/viewcontent.cgi?article=1027&context=leading-edge

Comparative Transcriptomic Analysis of Primary and Recurrent Ovarian Granulosa Cell Tumors

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