Comprehensive molecular characterization of human colon and rectal cancer

  title={Comprehensive molecular characterization of human colon and rectal cancer},
  author={Donna M. Muzny and Matthew N. Bainbridge and Kyle Chang and Huyen Dinh and Jennifer Drummond and Gerald R. Fowler and Christie L. Kovar and Lora L Lewis and Margaret B. Morgan and Irene Newsham and Jeffrey S. Reid and Jireh Santibanez and Eve Shinbrot and Lisa R. Trevi{\~n}o and Yuan-qing Wu and Min Wang and Preethi H. Gunaratne and Lawrence A. Donehower and Chad J. Creighton and David A. Wheeler and Richard A. Gibbs and Michael S. Lawrence and Douglas Voet and Rui Jing and Kristian Cibulskis and Andrey Y. Sivachenko and Petar Stojanov and Aaron McKenna and Eric S. Lander and S. Gabriel and Li Ding and Robert S. Fulton and Daniel C. Koboldt and Todd N. Wylie and Jason R. Walker and David J. Dooling and Lucinda Fulton and Kim D. Delehaunty and Catrina C. Fronick and Ryan T. Demeter and Elaine R. Mardis and Richard K. Wilson and Andy Chu and Hye-Jung E. Chun and Andrew J. Mungall and Erin D. Pleasance and A. Gordon Robertson and Dominik Stoll and Miruna Balasundaram and Inanç Birol and Yaron S. N. Butterfield and Eric Chuah and Robin J.N. Coope and Noreen Dhalla and Ranabir Guin and Carrie Hirst and Martin Hirst and Robert A. Holt and Darlene Lee and Haiyan Irene Li and Michael Mayo and Richard A. Moore and Jacqueline E. Schein and Jared R. Slobodan and Angela Tam and Nina Thiessen and Richard Varhol and Thomas Zeng and Yongjun Zhao and Steven J. M. Jones and Marco A. Marra and Adam J. Bass and Alex H. Ramos and Gordon Saksena and Andrew D. Cherniack and Steven E Schumacher and Barbara Tabak and Scott L. Carter and Nam Pho and Huy Nguyen and Roberto Onofrio and Andrew Crenshaw and Kristin G. Ardlie and Rameen Beroukhim and Wendy Winckler and Matthew L Meyerson and Alexei Protopopov and Angela Hadjipanayis and Eunjung Alice Lee and Ruibin Xi and Lixing Yang and Xiaojia Ren and Narayanan Sathiamoorthy and Peng-Chieh Chen and Psalm S Haseley and Yonghong Xiao and Semin Lee and Jonathan G. Seidman and Lynda Chin and Peter J. Park and Raju Kucherlapati and James T. Auman and Katherine A. Hoadley and Ying Du and Matthew D. Wilkerson and Yan Shi and Christina L. Liquori and Shaowu Meng and Ling Li and Yidi J. Turman and Michael D. Topal and Donghui Tan and Scot Michael Waring and Elizabeth Buda and Jesse L. Walsh and Corbin D. Jones and Piotr A. Mieczkowski and Darshan Singh and Junyuan Wu and Anisha Gulabani and Peter Dolina and Tom Bodenheimer and Alan Hoyle and Janae V. Simons and Matthew G. Soloway and Lisle E. Mose and Stuart R. Jefferys and Saianand Balu and Brian D. O’Connor and Jan Prins and Derek Y. Chiang and David Neil Hayes and Charles M. Perou and Toshinori Hinoue and Daniel J. Weisenberger and Dennis T. Maglinte and Fei Pan and Benjamin Paul Berman and David J. Van Den Berg and Hui Shen and Timothy J. Triche and Stephen B. Baylin and Peter W. Laird and Gad Getz and Michael S. Noble and Doug Voat and Nils Gehlenborg and Danielle M. Dicara and Juinhua Zhang and Hailei Zhang and Chang-Jiun Wu and Spring Yingchun Liu and Sachet A. Shukla and Lihua Zhou and Pei Lin and Richard W. Park and Marc-Danie Nazaire and James Robinson and Helga Thorvaldsd{\'o}ttir and Jill P. Mesirov and V{\'e}steinn Thorsson and Sheila M. Reynolds and Brady Bernard and Richard Kreisberg and Jake Lin and Lisa E. Iype and Ryan Bressler and Timo Erkkil{\"a} and Madhumati Gundapuneni and Yuexin Liu and Adam Norberg and Thomas Robinson and Da Yang and Wei Zhang and Ilya Shmulevich and Jorma J. de Ronde and Nikolaus D. Schultz and Ethan G. Cerami and Giovanni Domenico Ciriello and Arthur P. Goldberg and Benjamin E. Gross and Anders S. Jacobsen and Jianjiong Gao and Bogumił Kaczkowski and Rileen Sinha and B{\"u}lent Arman Aksoy and Yevgeniy Antipin and Boris Reva and Ronglai Shen and Barry S. Taylor and Marc Ladanyi and Chris Sander and Rehan Akbani and Nianxiang Zhang and Bradley M. Broom and Tod D. Casasent and Anna Unruh and Chris Wakefield and Stanley R. Hamilton and Ronald C Cason and Keith A. Baggerly and John N. Weinstein and David Haussler and Christopher C. Benz and Joshua M. Stuart and Stephen Charles Benz and J. Zachary Sanborn and Charles J. Vaske and Jingchun Zhu and Christopher Szeto and Gary K. Scott and Christina Yau and Sam Ng and Theodore Goldstein and Kyle Ellrott and Eric A. Collisson and Aaron E. Cozen and Daniel R. Zerbino and Christopher Wilks and Brian Craft and Paul T. Spellman and Robert J. Penny and Troy Shelton and Martha Hatfield and Scott Morris and Peggy Yena and Candace Shelton and Mark E. Sherman and Joseph D. Paulauskis and Julie M. Gastier-Foster and Jay Bowen and Nilsa C. Ramirez and Aaron D. Black and Robert Pyatt and Lisa Wise and Peter White and Monica M. Bertagnolli and Jennifer Brown and Timothy A. Chan and Gerald C. Chu and Christine Czerwinski and Frederick Denstman and Rajiv Dhir and Arnulf D{\"o}rner and Charles S. Fuchs and Jos{\'e} G. Guillem and Mary V. Iacocca and Hartmut Juhl and Andrew Kaufman and Bernard Kohl and Xuan Van Le and M. C. Mariano and Elizabeth N. Medina and Michael Meyers and Garrett Nash and Phillip B. Paty and Nicholas J. Petrelli and Brenda Rabeno and William G Richards and David B. Solit and Patricia Swanson and Larissa Temple and Joel E. Tepper and Richard A. Thorp and Efsevia Vakiani and Martin R. Weiser and Joseph E. Willis and Gary Witkin and Zhao-shi Zeng and Michael J. Zinner and Carsten Zornig and Mark A. Jensen and Robert Sfeir and Ari B. Kahn and Anna L. Chu and Prachi Kothiyal and Zhining Wang and E. E. Snyder and Joan U. Pontius and Todd Pihl and Brenda Ayala and Mark Backus and Jessica L Walton and John H. Whitmore and Julien Baboud and Dominique L. Berton and Matthew C. Nicholls and Deepak Srinivasan and Rohini Raman and Stanley Girshik and Peter A. Kigonya and Shelley Alonso and Rashmi N. Sanbhadti and Sean P. Barletta and John M. Greene and David Pot and Kenna R. Mills Shaw and Laura A. L. Dillon and Kenneth H. Buetow and Tanja Davidsen and John A. Demchok and Greg Eley and Martin L Ferguson and Peter Fielding and Carl F. Schaefer and Margi Sheth and Liming Yang and Mark Guyer and Bradley A Ozenberger and Jacqueline D. Palchik and Jane Peterson and Heidi J. Sofia and Elizabeth J. Thomson},
  pages={330 - 337}
To characterize somatic alterations in colorectal carcinoma, we conducted a genome-scale analysis of 276 samples, analysing exome sequence, DNA copy number, promoter methylation and messenger RNA and microRNA expression. A subset of these samples (97) underwent low-depth-of-coverage whole-genome sequencing. In total, 16% of colorectal carcinomas were found to be hypermutated: three-quarters of these had the expected high microsatellite instability, usually with hypermethylation and MLH1… 

Landscape of somatic single-nucleotide and copy-number mutations in uterine serous carcinoma

Analysis of whole-exome sequencing of 57 cancers identified frequent mutation of DNA damage, chromatin remodeling, cell cycle, and cell proliferation pathways in USC and suggest potential targets for treatment of this lethal variant of endometrial cancer.

Genomic Alterations of NTRK, POLE, ERBB2, and Microsatellite Instability Status in Chinese Patients with Colorectal Cancer

The results of this study provide an early support for the feasibility and utility of genomic profiling in Chinese patients with CRC.

Whole-genome sequencing and comprehensive molecular profiling identify new driver mutations in gastric cancer

A multidimensional and comprehensive genomic landscape that highlights the molecular complexity of gastric cancer and provides a road map to facilitate genome-guided personalized therapy is illustrated.

A genome‐wide study of the relationship between chromosomal abnormalities and gene expression in colorectal tumors

It is concluded that specific 13q and 22q CN gains with gene expression changes in the corresponding loci may play an important role in IMC cells' progression into invasive CRC.

Integrated genomic characterization of endometrial carcinoma

  • D. LevineGad Stacey B. Kristian Eric Andrey Carrie Mike Cyriac Getz Gabriel Cibulskis Lander Sivachenko Sougnez L H. Sofia
  • Biology, Medicine
  • 2013
The genomic features of endometrial carcinomas permit a reclassification that may affect post-surgical adjuvant treatment for women with aggressive tumours, and these features are classified into four categories: POLE ultramutated, microsatellite instability hypermutated, copy- number low, and copy-number high.

Novel recurrently mutated genes and a prognostic mutation signature in colorectal cancer

The application of next-generation sequencing has led to the identification of three novel significantly mutated genes in CRC and a mutation signature that predicts survival outcomes for stratifying patients with CRC independent of tumor-node-metastasis staging.

High Prevalence and Clinical Relevance of Genes Affected by Chromosomal Breaks in Colorectal Cancer

CNA-associated chromosomal breaks within genes represent a highly prevalent and clinically relevant subset of SVs in CRC and are concluded to represent one CRC subtype with very poor prognosis.

Whole genome sequencing of 2,023 colorectal cancers reveals mutational landscapes, new driver genes and immune interactions

The most detailed high-resolution map to date of somatic mutations in colorectal cancer is provided, and associations with clinicopathological features are demonstrated, in particular location in the large bowel.

Multilevel genomics of colorectal cancers with microsatellite instability—clinical impact of JAK1 mutations and consensus molecular subtype 1

Multilevel genomic analyses of MSI+ colorectal cancer revealed molecular heterogeneity with clinical relevance, including tumor immunogenicity and a favorable patient outcome associated with JAK1 mutations and the transcriptomic subgroup CMS1, emphasizing the potential for prognostic stratification of this clinically important subtype.

Mutation Profiling of Premalignant Colorectal Neoplasia

The mutation profiles of conventional colorectal adenomas (CNADs) across stages of progression towards early carcinoma were compared and a significant increase in copy number variant frequency was observed from LGD through HGD to malignant samples.



Comprehensive genomic characterization defines human glioblastoma genes and core pathways

The interim integrative analysis of DNA copy number, gene expression and DNA methylation aberrations in 206 glioblastomas reveals a link between MGMT promoter methylation and a hypermutator phenotype consequent to mismatch repair deficiency in treated gliobeasts, demonstrating that it can rapidly expand knowledge of the molecular basis of cancer.

Integrative genomics reveals mechanisms of copy number alterations responsible for transcriptional deregulation in colorectal cancer

A preponderance of chromosome breakpoints at sites of copy number variants (CNVs) in the CRC cell lines is revealed, a novel mechanism of DNA breakage in cancer.

Genomic sequencing of colorectal adenocarcinomas identifies a recurrent VTI1A-TCF7L2 fusion

Previously unidentified levels of genomic rearrangements in colorectal carcinoma that can lead to essential gene fusions and other oncogenic events are shown.

Genome-scale analysis of aberrant DNA methylation in colorectal cancer.

Four DNA methylation-based subgroups of CRC are identified using model-based cluster analyses and novel insight is provided regarding the role of CIMP-specific DNA hypermethylation in gene silencing.

Integrated Genomic Analyses of Ovarian Carcinoma

It is reported that high-grade serous ovarian cancer is characterized by TP53 mutations in almost all tumours (96%); low prevalence but statistically recurrent somatic mutations in nine further genes including NF1, BRCA1,BRCA2, RB1 and CDK12; 113 significant focal DNA copy number aberrations; and promoter methylation events involving 168 genes.

The Mutational Landscape of Head and Neck Squamous Cell Carcinoma

The results indicate the ability of large-scale sequencing to reveal fundamental tumorigenic mechanisms and suggest the development of targeted therapies for head and neck cancer may be hindered by complex mutational profiles.

Molecular genetics of colorectal cancer.

  • E. Fearon
  • Biology
    Annual review of pathology
  • 2011
The gene defects in CRC often target proteins and pathways that exert pleiotropic effects on the cancer cell phenotype, and particular genetic and epigenetic alterations are linked to biologically and clinically distinct subsets of CRC.

The Consensus Coding Sequences of Human Breast and Colorectal Cancers

The sequence of well-annotated human protein-coding genes in two common tumor types is determined to define the genetic landscape of two human cancer types, provide new targets for diagnostic and therapeutic intervention, and open fertile avenues for basic research in tumor biology.

Mutations in the WTX - gene are found in some high-grade microsatellite instable (MSI-H) colorectal cancers

Mutations in the WTX-gene might compromise the function of the β-CATENIN destruction complex in only a small fraction of MSI-H CRCs thus contributing to the process of carcinogenesis.

The Genomic Landscapes of Human Breast and Colorectal Cancers

It is concluded that the genomic landscapes of breast and colorectal cancers are composed of a handful of commonly mutated gene “mountains” and a much larger number of gene ‘hills’ that are mutated at low frequency.