Pathologist-initiated whole genome and transcriptome sequencing demonstrates diagnostic utility in resolving difficult-to-diagnose tumors

Vissers, JHA; Mitchell, C; Prall, OWJ; Lo, WY; Kanwal, S; Luen, SJ; Watts, SC; Angel, CM; Khoo, C; Pang, JB; Murray, WK; Snell, C; Christie, M; Rebello, RJ; Tothill, RW; Pham, K; Hofmann, O; Fox, SB; Grimmond, SM

Author(s): Vissers, JHA; Mitchell, C; Prall, OWJ; Lo, WY; Kanwal, S; Luen, SJ; Watts, SC; Angel, CM; Khoo, C; Pang, JB; Murray, WK; Snell, C; Christie, M; Rebello, RJ; Tothill, RW; Pham, K; Hofmann, O; Fox, SB; Grimmond, SM;
Details: Publication Year 2025-10-07,Volume 17,Issue #1,Page 107
Journal Title: Genome Medicine
Publication Type: Research article
Abstract: BACKGROUND: Despite significant advances in diagnostic cancer histopathology, a subset of tumors are unable to be classified using WHO criteria. The resulting diagnostic uncertainty can result in inappropriate clinical management and negative patient outcomes. METHODS: We investigated whether combining histopathology with whole genome and transcriptome sequencing (WGTS) could improve the classification of tumors that posed diagnostic dilemmas despite extensive histopathology and standard molecular work-up at a quaternary oncology center. RESULTS: We successfully sequenced 45 tumors from an initial set of 54 unclassified tumors (83% success rate). A confident diagnosis was made for 35/45 tumors (78%). Additionally, potential treatment targets were identified in 21/45 tumors (47%). Theoretical comparison with alternative assays demonstrated that WGTS was uniquely capable of detecting critical diagnostic findings in 9/35 tumors (26%). CONCLUSIONS: This work supports augmenting histopathology and standard molecular pathology with WGTS in the classification of difficult-to-diagnose tumors.
Publisher: BioMed Central
Keywords: Humans; *Neoplasms/diagnosis/genetics/pathology; *Transcriptome; *Whole Genome Sequencing; Gene Expression Profiling; Pathologists; Female; Diagnostic dilemma; Diagnostic histopathology; Next generation sequencing; Tumor classification; Whole genome and transcriptome sequencing
Department(s): Pathology; Medical Oncology
Publisher's Version: https://doi.org/10.1186/s13073-025-01534-5
Open Access at Publisher's Site: https://doi.org/10.1186/s13073-025-01534-5
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2025-11-25 12:06:37

Last Modified: 2025-11-25 12:06:47