Molecular tumor grading of non muscle invasive bladder cancer based on whole transcriptome analysis.

Medientyp: E-Artikel

Titel: Molecular tumor grading of non muscle invasive bladder cancer based on whole transcriptome analysis

Beteiligte: Shen, Jess; Noon, Aidan; LIU, Yu; Kuk, Cynthia; Ilczynski, C; Ni, R; Sukhu, B; Chan, K; Gunaratne, Adrian; Erlich, Annette; Cremer, Chris; Morris, Quaid; Barbosa-Morais, Nuno L; Fleshner, Neil Eric; Kulkarni, Girish S.; Blencowe, Ben; Azad, Azar; van der Kwast, Theodorus; Zlotta, Alexandre; Wrana, Jeff L

Erschienen: American Society of Clinical Oncology (ASCO), 2016

Sprache: Englisch

DOI: 10.1200/jco.2016.34.2_suppl.467

ISSN: 1527-7755; 0732-183X

Schlagwörter: Cancer Research ; Oncology

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Beschreibung: 467 Background: There is an unmet need for a comprehensive genomic characterization of non muscle invasive bladder cancer (NMIBC). NMIBC comprise over 70% of all bladder cancers at presentation. They have highly variable clinical behavior that is not always adequately predicted on the basis of their histological grade (2004 World Health Organization low and high grade, LG-HG). The discrepancy between phenotype and genotype is compounded further by interobserver variability in pathological grading. We have previously established methods for whole transcriptome RNAseq from formalin fixed paraffin embedded tissues (FFPE). Methods: Whole transcriptomic analysis of 110 NMI FFPE BC both LG and HG was performed incorporating messenger RNA expression, splice variants, gene fusion, and pathway perturbation. We used a discovery (n = 40) and a validation cohort (n = 70). These data were integrated and tested for correlation with both pathological grading and clinical outcomes. Grade Risk Index (GRI) score quantifying how closely a patient's transcriptome is related to a reference set of LG NMIBC samples was established. Conventional pathological grading was reviewed by 3 different expert uro-pathologists and interobserver variability calculated. Results: Unsupervised clustering of data from RNA sequencing uncovered classification of three robust - - nonoverlapping, prognostically significant subtypes of NMIBC with distinct GRIs and signatures. When applied by expert pathologists, interobserver variability in histological grading was observed in 17.5%. In the intermediate group (GRI 0.13 to 0.19), pathologists disagreed in 37.5% whether BC was LG or HG. HG NMIBC clustered with MIBC. LG NMIBC in the intermediate GRI group included either very bulky tumors or extremely rare metastatic LG BC (n = 4). HG disease was associated with a shift in BMP signaling and a germ stem cell-like phenotype. Multiple components of the centromere complex and APOBEC3B were upregulated in HG BC. FGFR3::TACC3 fusion events were observed in LG NMIBC only (11.5%). Conclusions: Whole transcriptomic sequencing data delineated three molecular classes of NMIBC.

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