Showing papers by "Rehan Akbani published in 2016"
University of Sannio1, VU University Amsterdam2, University of São Paulo3, University of California, Santa Cruz4, Harvard University5, Khalifa University6, Columbia University7, University of Texas MD Anderson Cancer Center8, Henry Ford Hospital9, Henry Ford Health System10, Baylor College of Medicine11, Memorial Sloan Kettering Cancer Center12, Emory University13, Ohio State University14, Case Western Reserve University15, University of California, San Francisco16, Princess Margaret Cancer Centre17, Van Andel Institute18, University of Washington19
TL;DR: The complete set of genes associated with 1,122 diffuse grade II-III-IV gliomas were defined from The Cancer Genome Atlas and molecular profiles were used to improve disease classification, identify molecular correlations, and provide insights into the progression from low- to high-grade disease.
1,535 citations
W. Marston Linehan1, Paul T. Spellman, Christopher J. Ricketts, Chad J. Creighton +224 more•Institutions (2)
TL;DR: Type 1 and type 2 papillary renal-cell carcinomas were shown to be different types of renal cancer characterized by specific genetic alterations, with type 2 further classified into three individual subgroups on the basis of molecular differences associated with patient survival.
Abstract: Background
Papillary renal cell carcinoma, accounting for 15% of renal cell carcinoma, is a heterogeneous disease consisting of different types of renal cancer, including tumors with indolent, multifocal presentation and solitary tumors with an aggressive, highly lethal phenotype. Little is known about the genetic basis of sporadic papillary renal cell carcinoma; no effective forms of therapy for advanced disease exist.
976 citations
TL;DR: Although targeted therapies for lung ADC and SqCC are largely distinct, immunotherapies may aid in treatment for both subtypes.
Abstract: Matthew Meyerson, Ramaswamy Govindan and colleagues examine the exome sequences and copy number profiles of 660 lung adenocarcinoma and 484 lung squamous cell carcinoma tumors. They identify novel significantly mutated genes and amplification peaks and find that around half of the tumors have at least five predicted neoepitopes.
858 citations
University of Texas MD Anderson Cancer Center1, Harvard University2, Massachusetts Institute of Technology3, Baylor College of Medicine4, University of North Carolina at Chapel Hill5, Johns Hopkins University6, University of Michigan7, University of São Paulo8, Institute for Systems Biology9, University of Lausanne10, Memorial Sloan Kettering Cancer Center11, Translational Genomics Research Institute12, University of California, Santa Cruz13, Brigham and Women's Hospital14, University Health Network15, BC Cancer Agency16, Brown University17, Ludwig Maximilian University of Munich18, Kolling Institute of Medical Research19, Royal North Shore Hospital20, National Institutes of Health21, Arizona State University22, University of Würzburg23
TL;DR: Integrated subtype analysis identified three ACC subtypes with distinct clinical outcome and molecular alterations which could be captured by a 68-CpG probe DNA-methylation signature, proposing a strategy for clinical stratification of patients based on molecular markers.
453 citations
Baylor College of Medicine1, Memorial Sloan Kettering Cancer Center2, University of Lausanne3, Harvard University4, Yale University5, Massachusetts Institute of Technology6, University of Texas MD Anderson Cancer Center7, Korea Institute of Science and Technology Information8, KAIST9, University of Wisconsin-Madison10, University of Kansas11, Tufts University12, Mayo Clinic13
TL;DR: Differences between the genomic subtypes suggest that therapeutic strategies could be tailored to each RCC disease subset.
295 citations
TL;DR: TCGA's RNASeq data represent one of the largest collections of cancer transcriptomes ever assembled, and the interface presents intuitive graphical representations of splicing patterns, read counts and various statistical summaries, including percent spliced in.
Abstract: TCGA's RNASeq data represent one of the largest collections of cancer transcriptomes ever assembled. RNASeq technology, combined with computational tools like our SpliceSeq package, provides a comprehensive, detailed view of alternative mRNA splicing. Aberrant splicing patterns in cancers have been implicated in such processes as carcinogenesis, de-differentiation and metastasis. TCGA SpliceSeq (http://bioinformatics.mdanderson.org/TCGASpliceSeq) is a web-based resource that provides a quick, user-friendly, highly visual interface for exploring the alternative splicing patterns of TCGA tumors. Percent Spliced In (PSI) values for splice events on samples from 33 different tumor types, including available adjacent normal samples, have been loaded into TCGA SpliceSeq. Investigators can interrogate genes of interest, search for the genes that show the strongest variation between or among selected tumor types, or explore splicing pattern changes between tumor and adjacent normal samples. The interface presents intuitive graphical representations of splicing patterns, read counts and various statistical summaries, including percent spliced in. Splicing data can also be downloaded for inclusion in integrative analyses. TCGA SpliceSeq is freely available for academic, government or commercial use.
251 citations
76 citations
TL;DR: RPPA technology has emerged as a robust, sensitive, cost-effective approach to the analysis of large numbers of samples for quantitative assessment of key members of functional pathways that are affected by tumor-targeting therapeutics.
51 citations
TL;DR: This study uncovers diverse mutational processes underlying the transition from early adenoma to cancer, which has broad implications for biomarker-driven targeting of CEA/TGF-β in high-risk adenomas and may lead to early detection of aggressive adanoma to CRC progression.
Abstract: Mutational processes and signatures that drive early tumorigenesis are centrally important for early cancer prevention. Yet, to date, biomarkers and risk factors for polyps (adenomas) that inordinately and rapidly develop into colon cancer remain poorly defined. Here, we describe surprisingly high mutational profiles through whole-genome sequence (WGS) analysis in 2 of 4 pairs of benign colorectal adenoma tissue samples. Unsupervised hierarchical clustered transcriptomic analysis of a further 7 pairs of adenomas reveals distinct mutational signatures regardless of adenoma size. Transitional single nucleotide substitutions of C:G>T:A predominate in the adenoma mutational spectrum. Strikingly, we observe mutations in the TGF-β pathway and CEA-associated genes in 4 out of 11 adenomas, overlapping with the Wnt pathway. Immunohistochemical labeling reveals a nearly 5-fold increase in CEA levels in 23% of adenoma samples with a concomitant loss of TGF-β signaling. We also define a functional role by which the CEA B3 domain interacts with TGFBR1, potentially inactivating the tumor suppressor function of TGF-β signaling. Our study uncovers diverse mutational processes underlying the transition from early adenoma to cancer. This has broad implications for biomarker-driven targeting of CEA/TGF-β in high-risk adenomas and may lead to early detection of aggressive adenoma to CRC progression.
18 citations
TL;DR: The data suggest that while some UCS tumors develop from an endometrioid lineage, the majority likely de-differentiate from a serous precursor, potentially accounting for their clinical aggressiveness and poor response to treatment.
Abstract: Proceedings: AACR 107th Annual Meeting 2016; April 16-20, 2016; New Orleans, LA
We used array- and sequencing-based technologies to perform an integrated genomic, epigenomic, transcriptomic, and proteomic characterization of the rare tumor type uterine carcinosarcoma (UCS) within the context of The Cancer Genome Atlas (TCGA) project using 57 cases that had stringent histopathologic review. Cohort samples had extensive copy number alterations and highly recurrent somatic mutations. Nearly all (91%) cases had TP53 mutations, similar to ovarian and serous uterine carcinomas, and frequent mutations were also found in PTEN, PIK3CA, PPP2R1A, FBXW7, and KRAS, similar to endometrioid and serous uterine carcinomas. Transcriptome sequencing identified a strong EMT gene signature in a subset of 17 (30%) cases, and cases with EMT signatures had decreased expression of mir-200 family members that was attributable to epigenetic alterations at miRNA promoters. The range of EMT signatures scores in UCS was the largest among all the TCGA tumor types studied. UCS shared proteomic features with both gynecologic carcinomas and non-gynecologic mesenchymal-like tumors. Our results indicate that UCS tumors share many features with serous-like endometrial carcinomas, including frequent TP53 mutations and extensive somatic copy number alterations, though with greater EMT features. Multiple somatic mutations and copy number alterations in genes that are therapeutic targets were identified. There was a high degree of mutational clonality, consistent with tumors being derived from a single cell of origin. Taken together, these data suggest that while some UCS tumors develop from an endometrioid lineage, the majority likely de-differentiate from a serous precursor, potentially accounting for their clinical aggressiveness and poor response to treatment.
Citation Format: Rehan Akbani, The Cancer Genome Atlas Research Network, Douglas A. Levine. Integrated molecular characterization of uterine carcinosarcoma in The Cancer Genome Atlas (TCGA) project. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 133.
4 citations
TL;DR: The integrated molecular analysis of 131 tumors in 2014 and the entire cohort of 412 tumors from the TCGA project in chemotherapy-naive muscle invasive urothelial bladder cancer are reported on, finding TP53 remained the most commonly mutated gene.
Abstract: 405 Background: We reported the integrated molecular analysis of 131 tumors in 2014 (Nature 507:315, 2014) and now report on the entire cohort of 412 tumors from the TCGA project in chemotherapy-naive muscle invasive urothelial bladder cancer. Methods: Following strict clinical and pathologic quality control, tumors were analyzed for DNA copy number variants, somatic mutations (WES), DNA methylation, mRNA, microRNA and (phospho-) protein expression, transcript splicing, gene fusions, viral integration, pathway perturbation, clinical correlates, and histopathology Results: There was a high overall somatic mutation rate (8.0/Mb), as previously reported, with a median of 245 and mean of 348 coding region mutations per sample. There were 54 significantly mutated genes (SMGs) (MutSig_2CV), increased from 32 in the original report. TP53 remained the most commonly mutated gene, and chromatin-modifying genes (MLL2, ARID1A, KDM6A) were also frequently mutated. KRAS, ERBB2, RB1, and ELF3 showed significant increase...