Laboratory of Translational Genomics

翻译基因组学实验室(LTG)对癌症的种系和体细胞遗传学进行研究，并对在癌症特异性全基因组关联研究(GWAS)和高危家庭中的连锁研究中确定的特定基因组区域进行分析。研究任务LTG的任务是了解种系和体细胞遗传变异对癌症病因和结果的贡献。它的主要目标是通过以下方式研究遗传变异区域：检测癌症易感等位基因使用序列分析和来自公共数据库的推论精细定位易感等位基因，通过对候选变异的生物信息学分析确定后续研究的优先顺序，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)调查与癌症易感性相关的常见遗传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)(前身为核心基因分型设备(CGF))一起开展全基因组关联研究(GWAS)，包括被称为CGEMS的项目(见下文)。LTG的研究人员使用来自评估数十万个单核苷酸多态(SNP)的大规模GWAS的数据，研究遗传标记与癌症风险之间的关联。为了了解这些关联背后的生物学基础，研究人员正在跟进重点验证研究、深度测序和功能分析，例如对表达水平和甲基化模式的分析。这项研究依赖于人口遗传学、流行病学和分子进化的多学科方法。实验室有一系列国际合作，收集癌症患者的材料和儿童和成人癌症的数据。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，这些工具可以处理从GWAS产生的大量基因数据。全基因组关联研究GWAS已在基因组中产生了近750个区域，与135种不同的疾病和特征有关。其中，135个区域与近20多种癌症有关，6个区域与多种癌症有关。为了更全面地了解这些新的发现，LTG的实验室研究正在进行中，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。通过这样做，研究人员提供了对致癌机制的功能和生物学见解。如果没有NCIS对Cohort Consortium的长期投资，这些努力是不可能的。Cohort Consortium是一个由来自41个不同人群的400万人组成的国际伙伴关系。这些队列提供了广泛的风险因素数据和生物样本，包括胚系DNA。易感性的癌症遗传标记(CGEMS)是一个合作项目，使用Gwas技术来调查几种类型的癌症、风险因素和结果，如癌症存活率。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的图谱，以便为进一步的功能研究提名合适的变异。LTG还在对其他恶性肿瘤进行基因分析，包括胰腺癌、膀胱癌和肺癌。伙伴关系和合作在下一波全基因组关联研究中发挥关键作用。为了获得必要的统计能力，以检测基因组变异和各种健康结果之间的关联，数据汇集已变得至关重要。高密度芯片和新兴技术现在允许对整个基因组中的数百万个SNP进行基因分型。LTG和许多NCI资助的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.