Comprehensive analysis of copy number variance and sensitivity to common targeted therapy in clear cell renal cell carcinoma: In silico analysis with in vitro validation.

Cancer Medicine
Yuqing LiChenchen Feng

Abstract

Chromosomal rearrangements are common in clear cell renal cell carcinoma (ccRCC) and their roles in mediating sensitivity to tyrosine kinase inhibitors (TKIs) and mTOR inhibitors (mTORi) remain elusive. We developed an in silico strategy by screening copy number variance (CNV) that was potentially related to TKI or mTORi sensitivity in ccRCC by reproducing the TCGA and GDSC datasets. Candidate genes should be both significantly prognostic and related to drug sensitivity or resistance, and were then validated in vitro. ADCYAP1 loss and GNAS gain were associated with sensitivity and resistance and to Cabozantinib, respectively. ACRBP gain and CTBP1 loss were associated with sensitivity and resistance and to Pazopanib, respectively. CDKN2A loss and SULT1A3 gain were associated with sensitivity and resistance and to Temsirolimus, respectively. CCNE1 gain was associated with resistance to Axitinib and LRP10 loss was associated with resistance to Sunitinib. Mutivariate analysis showed ADCYAP1, GNAS, and CCNE1 remained independently prognostic when adjusted for the rest. Here we show CNVs of several genes that are associated with sensitivity and resistance to commonly used TKIs and mTORi in ccRCC. Further validation and functional ana...Continue Reading

References

May 8, 2004·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Tae Won KimJung Shin Lee
Mar 2, 2006·Molecular and Cellular Biology·Seema PaliwalSteven R Grossman
Apr 7, 2006·Protein Science : a Publication of the Protein Society·Marco NardiniMartino Bolognesi
Aug 5, 2006·Annals of the New York Academy of Sciences·Norihito ShintaniAkemichi Baba
Jun 26, 2013·Nature Genetics·Yusuke SatoSeishi Ogawa
Sep 28, 2013·Nature Genetics·Travis I ZackRameen Beroukhim
Dec 24, 2014·Nature Reviews. Cancer·Lucy GossageEamonn R Maher
Apr 9, 2015·Current Osteoporosis Reports·Serap Turan, Murat Bastepe
Oct 22, 2016·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Ayse AyhanTian-Li Wang
Mar 10, 2017·Nature Reviews. Disease Primers·James J HsiehVincenzo Ficarra
May 10, 2017·Nature Reviews. Nephrology·Hiromi I WetterstenRobert H Weiss
Aug 5, 2017·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Lauren L RitterhouseFei Dong
Oct 17, 2017·The Journal of Clinical Investigation·Yao ZhanSonia V Del Rincón
Mar 11, 2018·Biochemical Pharmacology·Ahsan F BairamMing-Cheh Liu
Apr 11, 2018·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Caroline E McCoachRobert C Doebele
Jan 27, 2019·International Journal of Molecular Sciences·Chao-En WuChun-Nan Yeh

❮ Previous
Next ❯

Datasets Mentioned

BETA
339275820c1

Methods Mentioned

BETA
transfection
PCR

Software Mentioned

PrimerBank
cBioPortal
GDSC
cnaPANCAN

Related Concepts

Related Feeds

Adenocarcinoma, Clear Cell

Clear Cell Adenocarcinoma is a tumor that arises in the female genital tract and is characterized by cells that appear clear under the microscope. Discover the latest research here.