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, RB1, SPOP, TMPRSS2, TP53

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Scientific Background

The ForeSENTIA Prostate panel tests for single nucleotide variants, insertions, deletions, copy number alterations, and rearrangements in 36 genes which are commonly found in prostate cancers. Prostate cancer is the 2nd most common cancer in men and arises from the cells in the prostate gland. Prostate cancer initiates from the accumulation of mutations that will cause the healthy cells of the prostate to transform into malignant cells and divide uncontrollably.  Mutations in genes such as AR, TP53, BRCA1, and BRCA2 are only some examples of genes that are frequently mutated in prostate cancer patients. Therefore, screening for the mutations responsible for cancer progression enables the identification of FDA/EMA-approved therapies tailored for each patient.

 

Microsatellite instability (MSI), which can optionally be tested in this panel, has been detected in patients with prostate cancer and 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.

 

Recommendations by professional bodies:

ESMO recommends multigene tumor profiling via NGS on tumor samples for patients with advanced prostate cancer. The gene panels should also include MSI testing (Mosele et al., 2020)

 

References and more information: 

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

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.

Mosele F, Remon J, Mateo J, Westphalen CB, Barlesi F, Lolkema MP, Normanno N, Scarpa A, Robson M, Meric-Bernstam F, Wagle N, Stenzinger A, Bonastre J, Bayle A, Michiels S, Bièche I, Rouleau E, Jezdic S, Douillard JY, Reis-Filho JS, Dienstmann R, André F. Recommendations for the use of next-generation sequencing (NGS) for patients with metastatic cancers: a report from the ESMO Precision Medicine Working Group. Ann Oncol. 2020 Nov;31(11):1491-1505. doi: 10.1016/j.annonc.2020.07.014. Epub 2020 Aug 24. PMID: 32853681.

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, RB1, SPOP, TMPRSS2, TP53
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