Abstract:
BACKGROUND:Gynecologic malignancy is one of the leading causes of mortality in female adults worldwide. Comprehensive genomic analysis has revealed a list of molecular aberrations that are essential to tumorigenesis, progression, and metastasis of gynecologic tumors. However, targeting such alterations has frequently led to treatment failures due to underlying genomic complexity and simultaneous activation of various tumor cell survival pathway molecules. A compilation of molecular characterization of tumors with pharmacological drug response is the next step toward clinical application of patient-tailored treatment regimens. RESULTS:Toward this goal, we establish a library of 139 gynecologic tumors including epithelial ovarian cancers (EOCs), cervical, endometrial tumors, and uterine sarcomas that are genomically and/or pharmacologically annotated and explore dynamic pharmacogenomic associations against 37 molecularly targeted drugs. We discover lineage-specific drug sensitivities based on subcategorization of gynecologic tumors and identify TP53 mutation as a molecular determinant that elicits therapeutic response to poly (ADP-Ribose) polymerase (PARP) inhibitor. We further identify transcriptome expression of inhibitor of DNA biding 2 (ID2) as a potential predictive biomarker for treatment response to olaparib. CONCLUSIONS:Together, our results demonstrate the potential utility of rapid drug screening combined with genomic profiling for precision treatment of gynecologic cancers.
journal_name
Genome Bioljournal_title
Genome biologyauthors
Sa JK,Hwang JR,Cho YJ,Ryu JY,Choi JJ,Jeong SY,Kim J,Kim MS,Paik ES,Lee YY,Choi CH,Kim TJ,Kim BG,Bae DS,Lee Y,Her NG,Shin YJ,Cho HJ,Kim JY,Seo YJ,Koo H,Oh JW,Lee T,Kim HS,Song SY,Bae JS,Park WY,Han HDdoi
10.1186/s13059-019-1848-3subject
Has Abstractpub_date
2019-11-26 00:00:00pages
253issue
1eissn
1474-7596issn
1474-760Xpii
10.1186/s13059-019-1848-3journal_volume
20pub_type
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