title: Development and Application of a Microfluidics-Based Panel in the Basal/Luminal Transcriptional Characterization of Archival Bladder Cancers.
abstract: In the age of personalized medicine stratifying tumors into molecularly defined subtypes associated with distinctive clinical behaviors and predictable responses to therapies holds tremendous value. Towards this end, we developed a custom microfluidics-based bladder cancer gene expression panel for characterization of archival clinical samples. In silico analysis indicated that the content of our panel was capable of accurately segregating bladder cancers from several public datasets into the clinically relevant basal and luminal subtypes. On a technical level, our bladder cancer panel yielded robust and reproducible results when analyzing formalin-fixed, paraffin-embedded (FFPE) tissues. We applied our panel in the analysis of a novel set of 204 FFPE samples that included non-muscle invasive bladder cancers (NMIBCs), muscle invasive disease (MIBCs), and bladder cancer metastases (METs). We found NMIBCs to be mostly luminal-like, MIBCs to include both luminal- and basal-like types, and METs to be predominantly of a basal-like transcriptional profile. Mutational analysis confirmed the expected enrichment of FGFR3 mutations in luminal samples, and, consistently, FGFR3 IHC showed high protein expression levels of the receptor in these tumors. Our bladder cancer panel enables basal/luminal characterization of FFPE tissues and with further development could be used for stratification of bladder cancer samples in the clinic.
authors.affiliation: Oncology Biomarker Development, Genentech, South San Francisco, California, United States of America.
authors.forename: Doris
authors.initials: D
authors.lastname: Kim
authors.affiliation: Department of Biostatistics, Genentech, South San Francisco, California, United States of America.
authors.forename: YounJeong
authors.initials: Y
authors.lastname: Choi
authors.affiliation: Alternate Allele Consulting, Orinda, California, United States of America.
authors.forename: James
authors.initials: J
authors.lastname: Ireland
authors.affiliation: Department of Pathology, Genentech, South San Francisco, California, United States of America.
authors.forename: Oded
authors.initials: O
authors.lastname: Foreman
authors.affiliation: Oncology Biomarker Development, Genentech, South San Francisco, California, United States of America.
authors.forename: Rachel N
authors.initials: RN
authors.lastname: Tam
authors.affiliation: Oncology Biomarker Development, Genentech, South San Francisco, California, United States of America.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Patel
authors.affiliation: Oncology Biomarker Development, Genentech, South San Francisco, California, United States of America.
authors.forename: Erica B
authors.initials: EB
authors.lastname: Schleifman
authors.affiliation: Oncology Biomarker Development, Genentech, South San Francisco, California, United States of America.
authors.forename: Maipelo
authors.initials: M
authors.lastname: Motlhabi
authors.affiliation: Department of Pathology, Genentech, South San Francisco, California, United States of America.
authors.forename: Dorothy
authors.initials: D
authors.lastname: French
authors.affiliation: Oncology Biomarker Development, Genentech, South San Francisco, California, United States of America.
authors.forename: Cheryl V
authors.initials: CV
authors.lastname: Wong
authors.affiliation: Oncology Biomarker Development, Genentech, South San Francisco, California, United States of America.
authors.forename: Eric
authors.initials: E
authors.lastname: Peters
authors.affiliation: Oncology Biomarker Development, Genentech, South San Francisco, California, United States of America.
authors.forename: Luciana
authors.initials: L
authors.lastname: Molinero
authors.affiliation: Oncology Biomarker Development, Genentech, South San Francisco, California, United States of America.
authors.forename: Rajiv
authors.initials: R
authors.lastname: Raja
authors.affiliation: Oncology Biomarker Development, Genentech, South San Francisco, California, United States of America.
authors.forename: Lukas C
authors.initials: LC
authors.lastname: Amler
authors.affiliation: Oncology Biomarker Development, Genentech, South San Francisco, California, United States of America.
authors.forename: Garret M
authors.initials: GM
authors.lastname: Hampton
authors.affiliation: Oncology Biomarker Development, Genentech, South San Francisco, California, United States of America.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Lackner
authors.affiliation: Oncology Biomarker Development, Genentech, South San Francisco, California, United States of America.
authors.forename: Omar
authors.initials: O
authors.lastname: Kabbarah
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018070:Biological Specimen Banks; D015331:Cohort Studies; D003198:Computer Simulation; D005260:Female; D005557:Formaldehyde; D015972:Gene Expression Regulation, Neoplastic; D052138:Genes, Neoplasm; D006801:Humans; D008297:Male; D044085:Microfluidics / Q000379:methods*; D008875:Middle Aged; D016612:Paraffin Embedding; D015203:Reproducibility of Results; D016707:Tissue Fixation; D014158:Transcription, Genetic; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D005557:Formaldehyde