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Combined Tumor Suppressor Defects Characterize Clinically Defined Aggressive Variant Prostate Cancers
- Source :
- Clinical Cancer Research. 22:1520-1530
- Publication Year :
- 2016
- Publisher :
- American Association for Cancer Research (AACR), 2016.
-
Abstract
- Purpose: Morphologically heterogeneous prostate cancers that behave clinically like small-cell prostate cancers (SCPC) share their chemotherapy responsiveness. We asked whether these clinically defined, morphologically diverse, “aggressive variant prostate cancer (AVPC)” also share molecular features with SCPC. Experimental Design: Fifty-nine prostate cancer samples from 40 clinical trial participants meeting AVPC criteria, and 8 patient-tumor derived xenografts (PDX) from 6 of them, were stained for markers aberrantly expressed in SCPC. DNA from 36 and 8 PDX was analyzed by Oncoscan for copy number gains (CNG) and losses (CNL). We used the AVPC PDX to expand observations and referenced publicly available datasets to arrive at a candidate molecular signature for the AVPC. Results: Irrespective of morphology, Ki67 and Tp53 stained ≥10% cells in 80% and 41% of samples, respectively. RB1 stained Conclusions: Clinically defined AVPC share molecular features with SCPC and are characterized by combined alterations in RB1, Tp53, and/or PTEN. Clin Cancer Res; 22(6); 1520–30. ©2015 AACR.
- Subjects :
- Male
0301 basic medicine
Cancer Research
Pathology
medicine.medical_specialty
DNA Copy Number Variations
Biopsy
Article
03 medical and health sciences
Prostate cancer
0302 clinical medicine
Prostate
Biomarkers, Tumor
medicine
Cluster Analysis
Humans
PTEN
Missense mutation
Neoplasm Staging
biology
medicine.diagnostic_test
business.industry
Gene Expression Profiling
Tumor Suppressor Proteins
Prostatic Neoplasms
Cancer
medicine.disease
Immunohistochemistry
Gene expression profiling
030104 developmental biology
medicine.anatomical_structure
Oncology
Receptors, Androgen
030220 oncology & carcinogenesis
Mutation
Disease Progression
biology.protein
Cancer research
business
Signal Transduction
Subjects
Details
- ISSN :
- 15573265 and 10780432
- Volume :
- 22
- Database :
- OpenAIRE
- Journal :
- Clinical Cancer Research
- Accession number :
- edsair.doi.dedup.....0763bdfb2bd7b7bbc3a787bc6925abd1