Laboratory of Translational Genomics

翻译基因组学实验室（LTG）进行癌症的生殖系和体细胞遗传学研究，并分析在癌症特异性全基因组关联研究（GWAS）和高风险家族连锁研究中最终确定的基因组特定区域。研究使命LTG的使命是了解生殖系和体细胞遗传变异对癌症病因和结果的贡献。其主要目标是通过以下方式研究遗传变异的区域：检测癌症易感等位基因使用序列分析和公共数据库中的插补对易感等位基因进行精细定位通过候选变异的生物信息学分析对后续研究的变异进行优先排序通过实验室研究破译易感等位基因的生物学机制翻译基因组学实验室（LTG）研究与癌症易感性相关的常见遗传变异的生物学基础。该实验室与NCI的癌症基因组学研究实验室（CGR）（以前称为核心基因分型设施（CGF））一起进行全基因组关联研究（GWAS），包括称为CGEMS的项目（见下文）。LTG的研究人员正在研究遗传标记与癌症风险之间的关联，使用大规模GWAS的数据评估数十万个单核苷酸多态性（SNP）。为了了解这些关联背后的生物学，研究人员正在进行重点验证研究，深度测序和功能分析，如表达水平和甲基化模式分析。该研究依赖于群体遗传学、流行病学和分子进化的多学科方法。该实验室有一系列国际合作，收集儿童和成人癌症的癌症患者材料和数据。该实验室与NCI的CGR密切合作。CGR设计并进行高通量测序和基因分型，以支持癌症流行病学和遗传学部门内的大规模流行病学研究。CGR还参与了强大的生物信息学工具的开发，这些工具可以处理GWAS产生的大量基因型数据。全基因组关联研究GWAS已经在基因组中产生了与135种不同疾病和性状相关的近750个区域。其中，135个区域与近24种癌症相关，6个区域与多种癌症相关。为了更全面地了解这些新发现，LTG的实验室研究正在进行中，以通过验证，深度测序和翻译工作来确定导致这些关联的因果变异。在这样做的过程中，研究人员提供了功能和生物学的见解致癌机制。如果没有国家癌症研究所对队列联盟的长期投资，这些努力是不可能的，队列联盟是一个由来自41个队列的400万人组成的国际伙伴关系，由不同的人群组成。癌症易感性遗传标记（Cancer Genetic Markers of Susceptibility，CGEMS）是一个利用GWAS技术研究多种癌症类型、风险因素和结果（如癌症生存率）的合作项目。最近，该实验室专注于CGEMS前列腺癌和乳腺癌扫描的一系列后续研究。LTG的研究人员已经绘制了这些常见和不常见的遗传变异，以便为进一步的功能研究提名合适的变异。LTG还对其他恶性肿瘤进行遗传分析，包括胰腺癌、膀胱癌和肺癌。合作与协作合作与协作在下一波全基因组关联研究中发挥着关键作用。数据汇集已成为必不可少的，以实现必要的统计能力，以检测基因组变异和各种健康结果之间的关联。高密度芯片和新兴技术现在允许对基因组中数百万个SNP进行基因分型。LTG和许多NCI受资助研究组织之间的伙伴关系正在进行中，允许对致癌途径和基因-环境相互作用进行调查。

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.