Determination of TMPRSS2‐ERG, SPOP, FOXA1, and IDH1 prostate cancer molecular subtypes in Colombian patients and their possible implications for prognosis

• Published in: Cell biology international 2023-05, Vol.47 (5), p.1017-1030
• Main Authors: Montero‐Ovalle, Wendy, Sanabria‐Salas, María C., Mesa‐López de Mesa, Jorge, Varela‐Ramírez, Rodolfo, Segura‐Moreno, Yenifer Y., Sánchez‐Villalobos, Santiago A., Nuñez‐Lemus, Marcela, Serrano, Martha L.
• Format: Article
• Language: English
• Subjects: biomarker; Colombia; Fluorescence in situ hybridization; Hepatocyte Nuclear Factor 3-alpha - genetics; Humans; In Situ Hybridization, Fluorescence; Isocitrate Dehydrogenase; Male; Missense mutation; molecular subtypes; Mutation; mutations; Oncogene Proteins, Fusion - genetics; Paraffin; Prognosis; Prostate cancer; Prostatectomy; Prostatic Neoplasms - pathology; Repressor Proteins - genetics; Serine Endopeptidases; Statistical analysis; TMPRSS2‐ERG; Transcriptional Regulator ERG - genetics
• ISSN: 1065-6995; 1095-8355
• DOI: 10.1002/cbin.12000

Prostate cancer (PCa) is one of cancer with of the highest incidence and mortality worldwide. Current disease prognostic markers do not differentiate aggressive from indolent PCa with sufficient certainty, and characterization by molecular subtypes has been sought to allow a better classification. TMPRSS2‐ERG, SPOP, FOXA1, and IDH1 molecular subtypes have been described, but the association of these subtypes with prognosis in PCa is unclear; their frequency in Colombian patients is also unknown. Formalin‐fixed and paraffin‐embedded samples of radical prostatectomy from 112 patients with PCa were used. The TMPRSS2‐ERG subtype was assessed with fluorescent in situ hybridization. The mutations in SPOP, FOXA1, and IDH1 in hot‐spot regions were evaluated using Sanger sequencing. Fusion was detected in 71 patients (63.4%). No statistically significant differences were found between the state of fusion and the variables analyzed. In the 41 fusion‐negative cases (36.6%), two patients (4.9%) had missense mutations in SPOP (p.F102C and p.F133L), representing a 1.8% of the overall cohort. The low frequency of this subtype in Colombians could be explained by the reported variability in the frequency of these mutations according to the population (5%–20%). No mutations were found in FOXA1 in the cases analyzed. The synonym SNP rs11554137 IDH1105GGT was found in tumor tissue but not in the normal tissue in one case. A larger cohort of Colombian PCa patients is needed for future studies to validate these findings and gain a better understanding of the molecular profile of this cancer in our population and if there are any differences by Colombian regions.