Integrative molecular profiling of routine clinical prostate cancer specimens

Annals of Oncology : Official Journal of the European Society for Medical Oncology
Catherine S GrassoScott A Tomlins

Abstract

Comprehensive molecular profiling led to the recognition of multiple prostate cancer (PCa) molecular subtypes and driving alterations, but translating these findings to clinical practice is challenging. We developed a formalin-fixed paraffin-embedded (FFPE) tissue compatible integrative assay for PCa molecular subtyping and interrogation of relevant genetic/transcriptomic alterations (MiPC). We applied MiPC, which combines capture-based next generation sequencing and quantitative reverse transcription PCR (qRT-PCR), to 53 FFPE PCa specimens representing cases not well represented in frozen tissue cohorts, including 8 paired primary tumor and lymph node metastases. Results were validated using multiplexed PCR based NGS and Sanger sequencing. We identified known and novel potential driving, somatic mutations and copy number alterations, including a novel BRAF T599_V600insHT mutation and CYP11B2 amplification in a patient treated with ketoconazole (a potent CYP11B2 inhibitor). qRT-PCR integration enabled comprehensive molecular subtyping and provided complementary information, such as androgen receptor (AR) target gene module assessment in advanced cases and SPINK1 over-expression. MiPC identified highly concordant profiles for al...Continue Reading

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Citations

Jan 26, 2016·Neoplasia : an International Journal for Oncology Research·Yuanyuan QiaoTodd M Morgan
May 1, 2015·Neoplasia : an International Journal for Oncology Research·Daniel H HovelsonScott A Tomlins
Apr 12, 2015·Annals of Oncology : Official Journal of the European Society for Medical Oncology·G Attard, H Beltran
Jun 2, 2016·Nature Reviews. Clinical Oncology·Daniel E SprattScott A Tomlins
Nov 23, 2016·Nature Reviews. Clinical Oncology·Guilhem RoubaudDavid J Mulholland
May 1, 2018·Current Opinion in Urology·Simpa S SalamiAaron M Udager
Jan 10, 2018·Cold Spring Harbor Perspectives in Medicine·Aaron M Udager, Scott A Tomlins
Oct 18, 2016·The Cancer Journal·Daniel H Hovelson, Scott A Tomlins
Nov 6, 2018·JCI Insight·Simpa S SalamiGanesh S Palapattu
Jun 30, 2019·Cellular and Molecular Life Sciences : CMLS·Corinna KeupSabine Kasimir-Bauer
Mar 24, 2020·Nature Reviews. Urology·Marc Carceles-CordonJosep Domingo-Domenech
Aug 21, 2020·Nature Communications·R VatapalliS A Abdulkadir
Apr 10, 2019·Nature Reviews. Urology·Kevin M KooMatt Trau
Sep 28, 2018·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Daniel Nava RodriguesJohann S de Bono
Feb 18, 2018·Molecular Cancer Research : MCR·Udit SinghalTodd M Morgan

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