SCIENTIFIC BACKGROUND

AKT1, APC, AR, ATM, BARD1, BRAF, BRCA1, BRCA2, CHEK2, CTNNB1, ERBB2, FGFR1, FGFR2, FGFR3, FOXA1, MLH1, MSH2, MSH6, MYC, MYCN, NRAS, NTRK1, NTRK2, NTRK3, PALB2, PIK3CA, PIK3CB, PMS2, POLE, PTEN, RAD51C, RAD51D, SPOP, TMPRSS2, TP53

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Scientific Background

Prostate cancer arises from the cells in the prostate gland, and it is the 2nd most common cancer in men. Prostate cancer manifests from the accumulation of mutations that cause the healthy cells of the prostate to transform into malignant cells and divide uncontrollably.  The cancer cells will then form a tumor mass that will ultimately spread to nearby organs in a process known as metastasis. This panel identifies the genetic mutations in the circulating tumor DNA that is released from prostate cancers. Screening for the mutations responsible for cancer progression enables the identification of FDA/EMA approved therapies tailored to each patient with prostate cancer.

 

Microsatellite instability (MSI) immunotherapy biomarker has also been detected in patients with prostate cancer, and it can be used as an immunotherapy biomarker for men with advanced prostate cancer. The FDA approved drug pembrolizumab can be used as an immunotherapy option for MSI-high patients.

 

How many genes are tested in this panel?

35 genes

 

Recommendations by professional bodies

ESMO recommends liquid biopsy testing for mutations in BRCA1, BRCA2 or ATM genes for patients with advanced prostate cancer and might be eligible for PARP inhibitor therapy (Pascual et al., 2022; ESMO recommendations).

 

References and more information: 

Information obtained from professional bodies including National Cancer Institute, World Cancer Research Fund International

Pascual J, Attard G, Bidard FC, Curigliano G, De Mattos-Arruda L, Diehn M, Italiano A, Lindberg J, Merker JD, Montagut C, Normanno N, Pantel K, Pentheroudakis G, Popat S, Reis-Filho JS, Tie J, Seoane J, Tarazona N, Yoshino T, Turner NC. ESMO recommendations on the use of circulating tumour DNA assays for patients with cancer: a report from the ESMO Precision Medicine Working Group. Ann Oncol. 2022 Aug;33(8):750-768. doi: 10.1016/j.annonc.2022.05.520. Epub 2022 Jul 6. PMID: 35809752.

Shimizu K, Sano T, Mizuno K, Sunada T, Makita N, Hagimoto H, Goto T, Sawada A, Fujimoto M, Ichioka K, Ogawa O, Kobayashi T, Akamatsu S. A case of microsatellite instability-high clinically advanced castration-resistant prostate cancer showing a remarkable response to pembrolizumab sustained over at least 18 months. Cold Spring Harb Mol Case Stud. 2022 Jun 22;8(4):a006194. doi: 10.1101/mcs.a006194. PMID: 35487690; PMCID: PMC9235847.

Hempelmann JA, Lockwood CM, Konnick EQ, Schweizer MT, Antonarakis ES, Lotan TL, Montgomery B, Nelson PS, Klemfuss N, Salipante SJ, Pritchard CC. Microsatellite instability in prostate cancer by PCR or next-generation sequencing. J Immunother Cancer. 2018 Apr 17;6(1):29. doi: 10.1186/s40425-018-0341-y. PMID: 29665853; PMCID: PMC5904988.

GENES

AKT1, APC, AR, ATM, BARD1, BRAF, BRCA1, BRCA2, CHEK2, CTNNB1, ERBB2, FGFR1, FGFR2, FGFR3, FOXA1, MLH1, MSH2, MSH6, MYC, MYCN, NRAS, NTRK1, NTRK2, NTRK3, PALB2, PIK3CA, PIK3CB, PMS2, POLE, PTEN, RAD51C, RAD51D, SPOP, TMPRSS2, TP53
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