Whole-exome sequencing of cervical carcinomas identifies activating ERBB2 and PIK3CA mutations as targets for combination therapy
Zammataro L, Lopez S, Bellone S, Pettinella F, Bonazzoli E, Perrone E, Zhao S, Menderes G, Altwerger G, Han C, Zeybek B, Bianchi A, Manzano A, Manara P, Cocco E, Buza N, Hui P, Wong S, Ravaggi A, Bignotti E, Romani C, Todeschini P, Zanotti L, Odicino F, Pecorelli S, Donzelli C, Ardighieri L, Angioli R, Raspagliesi F, Scambia G, Choi J, Dong W, Bilguvar K, Alexandrov LB, Silasi DA, Huang GS, Ratner E, Azodi M, Schwartz PE, Pirazzoli V, Stiegler AL, Boggon TJ, Lifton RP, Schlessinger J, Santin AD. Whole-exome sequencing of cervical carcinomas identifies activating ERBB2 and PIK3CA mutations as targets for combination therapy. Proceedings Of The National Academy Of Sciences Of The United States Of America 2019, 116: 22730-22736. PMID: 31624127, PMCID: PMC6842590, DOI: 10.1073/pnas.1911385116.Peer-Reviewed Original ResearchConceptsPI3K/AKT/mTOR pathwaySquamous cell carcinomaWhole-exome sequencingAKT/mTOR pathwayPrimary cervical cancer cell linesPIK3CA inhibitorsRecurrent cervical cancer patientsMTOR pathwayCombination of copanlisibCervical cancer patientsPI3K/Akt/mTORCervical cancer xenograftsRegression of tumorsCervical cancer cell linesCervical tumor cell linesSingle nucleotide variantsWild-type tumorsRecurrent somatic missense mutationsAkt/mTORCell linesPan-HERCancer cell linesTypes 16/18Cervical cancerCancer patientsMutations in ILK, encoding integrin-linked kinase, are associated with arrhythmogenic cardiomyopathy
Brodehl A, Rezazadeh S, Williams T, Munsie NM, Liedtke D, Oh T, Ferrier R, Shen Y, Jones SJM, Stiegler AL, Boggon TJ, Duff HJ, Friedman JM, Gibson WT, Consortium F, Childs SJ, Gerull B. Mutations in ILK, encoding integrin-linked kinase, are associated with arrhythmogenic cardiomyopathy. Translational Research 2019, 208: 15-29. PMID: 30802431, PMCID: PMC7412573, DOI: 10.1016/j.trsl.2019.02.004.Peer-Reviewed Original ResearchConceptsIntegrin-linked kinase geneFirst LIM domainIntegrin-linked kinaseLIM domainsActin cytoskeletonRat myoblast cellsZebrafish showKinase geneCytoplasmic localizationDisease genesArrhythmogenic cardiomyopathyLife-threatening ventricular arrhythmiasMyoblast cellsJunctional proteinsHuman variantsILKSudden cardiac deathGenesFibro-fatty replacementNormal cardiac functionHalf of casesFunctional evidenceHeart muscle disorderMissense variantsDe novo