2017
Assigning clinical meaning to somatic and germ-line whole-exome sequencing data in a prospective cancer precision medicine study
Ghazani AA, Oliver NM, St. Pierre JP, Garofalo A, Rainville IR, Hiller E, Treacy DJ, Rojas-Rudilla V, Wood S, Bair E, Parello M, Huang F, Giannakis M, Wilson FH, Stover EH, Corsello SM, Nguyen T, Rana HQ, Church AJ, Lowenstein C, Cibulskis C, Amin-Mansour A, Heng J, Brais L, Santos A, Bauer P, Waldron A, Lo P, Gorman M, Lydon CA, Welch M, McNamara P, Gabriel S, Sholl LM, Lindeman NI, Garber JE, Joffe S, Van Allen EM, Gray SW, Jänne P, Garraway LA, Wagle N. Assigning clinical meaning to somatic and germ-line whole-exome sequencing data in a prospective cancer precision medicine study. Genetics In Medicine 2017, 19: 787-795. PMID: 28125075, DOI: 10.1038/gim.2016.191.Peer-Reviewed Original ResearchConceptsClinical evidenceCancer precision medicineWhole-exome sequencing dataPrecision medicineMolecular tumor boardTumor biopsy samplesGerm-line alterationsGerm-line variantsProtocol-based approachPrecision medicine studiesMetastatic colorectalPatient preferencesTumor boardLung adenocarcinomaClinical careBlood samplesBiopsy samplesClinical relevanceClinical teamClinical meaningTherapeutic relevanceUnknown significanceVariant reviewMedicine studiesGenomic alterations
2016
MTAP deletion confers enhanced dependency on the PRMT5 arginine methyltransferase in cancer cells
Kryukov GV, Wilson FH, Ruth JR, Paulk J, Tsherniak A, Marlow SE, Vazquez F, Weir BA, Fitzgerald ME, Tanaka M, Bielski CM, Scott JM, Dennis C, Cowley GS, Boehm JS, Root DE, Golub TR, Clish CB, Bradner JE, Hahn WC, Garraway LA. MTAP deletion confers enhanced dependency on the PRMT5 arginine methyltransferase in cancer cells. Science 2016, 351: 1214-1218. PMID: 26912360, PMCID: PMC4997612, DOI: 10.1126/science.aad5214.Peer-Reviewed Original ResearchConceptsProtein arginine methyltransferase 5Methylthioadenosine phosphorylaseCancer cell linesMultiple cancer lineagesPutative drug targetsCell linesTumor suppressor geneComprehensive genomic profilingCancer cell dependenciesEnzyme methylthioadenosine phosphorylaseArginine methyltransferaseCancer lineagesFunctional characterizationCancer dependenciesPRMT5 inhibitorsSuppressor geneDrug targetsTherapeutic strategiesPreferential impairmentMTAP deletionEnzymatic activityGenomic alterationsGenomic profilingCell dependencyCancer cells