Differentially methylated genes and androgen receptor re-expression in small cell prostate carcinomas

Epigenetics : Official Journal of the DNA Methylation Society
Brittany KlebAna Aparicio

Abstract

Small cell prostate carcinoma (SCPC) morphology is rare at initial diagnosis but often emerges during prostate cancer progression and portends a dismal prognosis. It does not express androgen receptor (AR) or respond to hormonal therapies. Clinically applicable markers for its early detection and treatment with effective chemotherapy are needed. Our studies in patient tumor-derived xenografts (PDX) revealed that AR-negative SCPC (AR(-)SCPC) expresses neural development genes instead of the prostate luminal epithelial genes characteristic of AR-positive castration-resistant adenocarcinomas (AR(+)ADENO). We hypothesized that the differences in cellular lineage programs are reflected in distinct epigenetic profiles. To address this hypothesis, we compared the DNA methylation profiles of AR(-) and AR(+) PDX using methylated CpG island amplification and microarray (MCAM) analysis and identified a set of differentially methylated promoters, validated in PDX and corresponding donor patient samples. We used the Illumina 450K platform to examine additional regions of the genome and the correlation between the DNA methylation profiles of the PDX and their corresponding patient tumors. Struck by the low frequency of AR promoter methylatio...Continue Reading

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Citations

Oct 30, 2016·Proceedings of the National Academy of Sciences of the United States of America·Fortunato FerraraWadih Arap
Mar 2, 2017·Nature Reviews. Urology·Takahiro InoueOsamu Ogawa
Apr 1, 2017·Current Oncology Reports·Panagiotis J VlachostergiosHimisha Beltran
May 31, 2018·Cold Spring Harbor Perspectives in Medicine·Loredana PucaHimisha Beltran
Jul 31, 2019·The Journal of Clinical Investigation·Mark P LabrecqueColm Morrissey
May 6, 2017·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Jieping HuTing Sun
Apr 25, 2018·Proceedings of the National Academy of Sciences of the United States of America·John K LeeOwen N Witte
Mar 27, 2018·The Prostate·W Nathaniel Brennen, John T Isaacs
Jun 21, 2018·Nature Communications·Loredana PucaHimisha Beltran
Jan 10, 2021·Oncogene·Nicolò FormaggioJean-Philippe Theurillat
Jan 13, 2021·Current Oncology Reports·Yasutaka Yamada, Himisha Beltran
Feb 6, 2021·Seminars in Cancer Biology·Sakshi GoelBushra Ateeq
Jul 10, 2018·Biochimica Et Biophysica Acta. Reviews on Cancer·Rama SoundararajanSendurai A Mani
Jul 23, 2021·Nature Reviews. Urology·Yong WangYuzhuo Wang
Aug 6, 2021·Oncogene·Su H ParkJindan Yu
Sep 8, 2021·Nature Cell Biology·Li Xin
Oct 1, 2021·Journal of Experimental & Clinical Cancer Research : CR·Shangwei ZhongJun-Li Luo

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Methods Mentioned

BETA
biopsy
biopsies
xenografts
xenograft
PCR
immunoprecipitation
MDA
electrophoresis
ChIP
ChIP-PCR

Software Mentioned

GraphPad
MCAM
LOWESS
GENE
GraphPad Prism
Primer Express

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