January 1, 2024

Rare, Novel, and Actionable Genomic Alterations in a Case of Prostatic Adenocarcinoma: Findings from a Molecular Tumor Board

Key Points

NTRK fusion was identified in prostatic adenocarcinoma, indicating a unique genomic alteration.
Comprehensive genomic profiling uncovered mutations in key genes like BRCA2 and alterations in the androgen receptor.
A multi-disciplinary tumor board guided treatment decisions, suggesting PARP inhibitor use based on genomic findings.
This case marks the first published report of an NTRK2 fusion in prostatic adenocarcinoma, highlighting its rarity.

Abstract

ABSTRACT Prostate cancer (PCa) accounts for 34,540 cases and 16,783 deaths annually among Indian males according to GLOBOCAN 2020. Comprehensive genomic profiling (CGP) can assist in identification of novel therapeutic targets and deployment of personalized therapies in cases with disease progression on standard treatment protocols. Genomic analysis of Pca cohorts has provided in-depth comprehension of genes and pathways involved in tumorigenesis and disease progression/ metastasis. In tandem with the discovery and development of novel therapies, repurposing of existing anti-cancer therapeutics has demonstrated a downward trend in Pca globally. Fusion of Neurotrophic Tyrosine Receptor Kinase (NTRK) constitute a group of tissue agnostic markers observed at varying frequencies in a spectrum of malignancies. NTRK1, 2, and 3 gene rearrangements leading to novel gene fusions have been detected in more than twenty different types of tumours including lung adenocarcinoma, colon adenocarcinoma and malignant melanoma. Uncommon cancers such as infantile/ congenital fibrosarcoma, secretory breast cancer, congenital mesoblastic nephroma have demonstrated NTRK fusions in >70% of these lesions. Here, we present a case of NTRK2 fusion positive prostatic adenocarcinoma with aggressive clinical disease and histopathology. CGP revealed AR (androgen receptor) splice variant mutations, BRCA2 (breast cancer gene 2) mutation, ERBB2 (Human Epidermal Growth Factor Receptor 2), MDM2 (Mouse double minute 2 homolog), MET (hepatocyte growth factor receptor) and MYC amplifications in addition to CDK19 5’: NTRK2 3’ translocation. The clinical progression of disease on androgen inhibitor therapy led to discussion in the treating hospital multi-disciplinary tumour board and decision to initiate treatment with PARP (poly-ADP ribose polymerase) inhibitor (PARPi) Olaparib was suggested. To our knowledge, this current case is the first published case report of a NTRK2 fusion in Pca.

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