Cancer

Cancer is among the most-common causes of death in Mexico, and incidence of the disease is on the rise worldwide. The SIGMA project aims to develop novel biomedical approaches to treat this devastating disease by applying powerful sequencing technologies to discover the genes and key pathways underlying common varieties of cancer. In first phase of the project, SIGMA researchers identified new genetic drivers of breast cancer, cervical cancer – both with special emphasis on patients in Mexico – lymphoma, head and neck cancer, sarcoma and several types of pediatric cancers. Today, in addition to continued genomic efforts, SIGMA researchers are translating those initial discoveries into therapeutic “roadmaps” of the disease, which will help speed the development of new cancer therapies to benefit patients in Mexico and beyond.

Publications

• Nat Genet, 2017: Computational correction of copy number effect improves specificity of CRISPR-Cas9 essentiality screens in cancer cells.
• Cell Syst, 2017: A Community Challenge for Inferring Genetic Predictors of Gene Essentialities through Analysis of a Functional Screen of Cancer Cell Lines.
• Gigascience, 2017: A dataset of images and morphological profiles of 30,000 small-molecule treatments using the Cell Painting assay.
• Cell, 2017: Defining a Cancer Dependency Map.
• Nature, 2017: Recurrent and functional regulatory mutations in breast cancer.
• Elife, 2017: Systematic morphological profiling of human gene and allele function via Cell Painting
• Cell Rep, 2016: Phenotypic Characterization of a Comprehensive Set of MAPK1/ERK2 Missense Mutants
• Cancer Discovery, 2016: Genomic Copy Number Dictates a Gene-Independent Cell Response to CRISPR/Cas9 Targeting
• Cell Syst. 2016: Genetic and Proteomic Interrogation of Lower Confidence Candidate Genes Reveals Signaling Networks in β-Catenin-Active Cancers
• Cancer Cell, 2016: High-throughput Phenotyping of Lung Cancer Somatic Mutations
• Cancer Discovery, 2016: Systematic functional interrogation of rare cancer variants identifies oncogenic alleles
• Blood, December 2015: Targetable genetic features of primary testicular and primary central nervous system lymphomas
• Nature genetics, November 2015: The genomic landscape of juvenile myelomonocytic leukemia
• PloS One, July 2015: Morphological Profiles of RNAi-Induced Gene Knockdown Are Highly Reproducible but Dominated by Seed Effects
• Genes, chromosomes & cancer, July 2015: Near universal detection of alterations in CTNNB1 and Wnt pathway regulators in desmoid-type fibromatosis by whole-exome sequencing and genomic analysis
• PLoS One, January 2015: A Maltose-Binding Protein Fusion Construct Yields a Robust Crystallography Platform for MCL1
• PNAS, December 2014: Complementary genomic approaches highlight the PI3K/mTOR pathway as a common vulnerability in osteosarcoma
• ACS medicinal chemistry letters, December 2014: Single Diastereomer of a Macrolactam Core Binds Specifically to Myeloid Cell Leukemia 1 (MCL1)
• Cancer discovery, September 2014: The Genomic Landscape of Pediatric Ewing Sarcoma
• Oncogene, June 2014: Exome sequencing of pleuropulmonary blastoma reveals frequent biallelic loss of TP53 and two hits in DICER1 resulting in retention of 5p-derived miRNA hairpin loop sequences
• Nature Genetics, January 2013: Whole exome sequencing identifies a recurrent NAB2-STAT6 fusion in solitary fibrous tumors
• Nature, December 2013: Landscape of genomic alterations in cervical carcinomas
• Nature, June 2013: Mutational heterogeneity in cancer and the search for new cancer genes
• Journal of Clinical Investigation, July 2012: A remarkably simple genome underlies highly malignant pediatric rhabdoid cancers
• Nature, June 2012: Sequence analysis of mutations and translocations across breast cancer subtypes
• PNAS, February 2012: Discovery and prioritization of somatic mutations in diffuse large B-cell lymphoma (DLBCL) by whole exome sequencing
• Science, July 2011: The mutational landscape of head and neck squamous cell carcinoma

Broad news stories

• October 2017: Editing false positives from cancer dependency maps drawn with CRISPR
• July 2017: Here there be dependencies: Putting cancers’ vulnerabilities on the map
• June 2017: The breast cancer genome’s “dark matter” starts to give up some secrets
• July 2016: Taking aim at rare cancer variants
• December 2013: International team completes systematic, genomic study of cervical cancer
• June 2013: Bringing out the usual – and unusual – cancer genomics suspects
• June 2012: Breast cancer’s many drivers
• July 2011: Convergence in head and neck cancer