The Laboratory of Translational Genomics (LTG) conducts studies on germline and somatic genetics of cancer and analyses on particular regions of the genome conclusively identified in cancer-specific genome-wide association studies (GWAS) and linkage studies in high-risk families.Research Mission LTG's mission is to understand the contribution of germline and somatic genetic variation to cancer etiology and outcomes. Its primary goals are to investigate regions of genetic variation by:Detecting cancer susceptibility alleles Fine mapping of susceptibility alleles using sequence analysis and imputation from public databases Prioritizing variants for follow-up studies through bioinformatic analysis of candidate variants Deciphering the biological mechanisms underlying susceptibility alleles through laboratory investigationThe Laboratory of Translational Genomics (LTG) investigates the biological basis of common inherited genetic variants associated with cancer susceptibility. Together with NCI's Cancer Genomics Research Laboratory (CGR), formerly known as the Core Genotyping Facility (CGF), the Laboratory carries out genome-wide association studies (GWAS), including the project known as CGEMS (see below).Using data from large-scale GWAS that evaluate hundreds of thousands of single nucleotide polymorphisms (SNPs), investigators at the LTG are studying the associations between genetic markers and cancer risk. To understand the biology underlying these associations, investigators are following up with focused validation studies, deep-sequencing, and functional analyses, such as analyses of expression levels and methylation patterns. This research relies on multidisciplinary approaches from population genetics, epidemiology and molecular evolution.The Laboratory has a series of international collaborations collecting cancer patient material and data for pediatric and adult cancers.The Laboratory works closely with the NCI's CGR. CGR designs and conducts high throughput sequencing and genotyping in support of large-scale epidemiologic studies within the Division of Cancer Epidemiology and Genetics. CGR is also involved in the development of powerful bioinformatics tools that handle high volume genotype data generated from GWAS.Genome-Wide Association Studies GWAS have yielded close to 750 regions in the genome associated with 135 different diseases and traits. Of these, 135 regions are associated with nearly two dozen cancers, and six regions are associated with multiple cancers. To more fully understand these novel findings, laboratory studies at the LTG are underway to identify the causal variants responsible for these associations through validation, deep sequencing, and translational work. In doing so, researchers are providing functional and biological insights into the mechanisms of carcinogenesis.These efforts would not be possible without NCIs long term investment in the Cohort Consortium, an international partnership of four million people from 41 cohorts, comprised of diverse populations. The cohorts provide extensive risk factor data and biospecimens, including germline DNA.Cancer Genetic Markers of SusceptibilityCancer Genetic Markers of Susceptibility (CGEMS) is a collaborative project employing GWAS technologies to investigate several types of cancer, risk factors, and outcomes such as cancer survival.Recently, the Laboratory has focused on a series of follow-up studies from CGEMS prostate and breast cancer scans. Investigators at the LTG have mapped those common and uncommon genetic variants in order to nominate suitable variants for further functional studies. The LTG is also conducting genetic analyses for other malignancies, including cancer of the pancreas, bladder and lung.Partnerships and CollaborationsCollaborations and partnerships play a pivotal role in the next wave of genome-wide association studies. Data pooling has become essential in order to achieve the statistical power necessary to detect associations between genomic variants and a variety of health outcomes. High-density chips and emerging technologies now allow the genotyping of millions of SNPs across the genome. Partnerships between the LTG and numerous NCI grantee research organizations are underway , allowing investigation into carcinogenic pathways and gene-environment interactions.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIACP010201-06
Application #
9154218
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
2015
Total Cost
Indirect Cost
Name
Cancer Epidemiology and Genetics
Department
Type
DUNS #
City
State
Country
Zip Code
Tang, Wei; Wallace, Tiffany A; Yi, Ming et al. (2018) IFNL4-?G Allele Is Associated with an Interferon Signature in Tumors and Survival of African-American Men with Prostate Cancer. Clin Cancer Res 24:5471-5481
Cobo, Isidoro; Martinelli, Paola; Flández, Marta et al. (2018) Transcriptional regulation by NR5A2 links differentiation and inflammation in the pancreas. Nature 554:533-537
Lou, Hong; Gharzouzi, Eduardo; Guerra, Sarita Polo et al. (2018) Low-cost HPV testing and the prevalence of cervical infection in asymptomatic populations in Guatemala. BMC Cancer 18:562
Klein, Alison P; Wolpin, Brian M; Risch, Harvey A et al. (2018) Genome-wide meta-analysis identifies five new susceptibility loci for pancreatic cancer. Nat Commun 9:556
Minas, Tsion Zewdu; Tang, Wei; Smith, Cheryl J et al. (2018) IFNL4-?G is associated with prostate cancer among men at increased risk of sexually transmitted infections. Commun Biol 1:191
Streicher, Samantha A; Klein, Alison P; Olson, Sara H et al. (2017) Impact of Sixteen Established Pancreatic Cancer Susceptibility Loci in American Jews. Cancer Epidemiol Biomarkers Prev 26:1540-1548
Samimi, Goli; Bernardini, Marcus Q; Brody, Lawrence C et al. (2017) Traceback: A Proposed Framework to Increase Identification and Genetic Counseling of BRCA1 and BRCA2 Mutation Carriers Through Family-Based Outreach. J Clin Oncol 35:2329-2337
Ricks-Santi, Luisel; McDonald, J Tyson; Gold, Bert et al. (2017) Next Generation Sequencing Reveals High Prevalence of BRCA1 and BRCA2 Variants of Unknown Significance in Early-Onset Breast Cancer in African American Women. Ethn Dis 27:169-178
Makowski, Matthew M; Willems, Esther; Fang, Jun et al. (2016) An interaction proteomics survey of transcription factor binding at recurrent TERT promoter mutations. Proteomics 16:417-26
Paquin, Ashley; Onabajo, Olusegun O; Tang, Wei et al. (2016) Comparative Functional Analysis of 12 Mammalian IFN-?4 Orthologs. J Interferon Cytokine Res 36:30-6

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