Exome-wide screening for common mutations in lymphoma

描述(申请人提供)：弥漫性大B细胞淋巴瘤(DLBCL)是最常见的淋巴瘤形式，占所有非霍奇金淋巴瘤病例的近40%。该病表现出显著的临床异质性。只有不到一半的患者通过标准的多药剂化疗治愈。另一方面，当使用相同的方案治疗时，超过一半的患者经历了疾病的早期进展、复发和死亡。近30年来，治疗这种疾病的化疗方案几乎没有变化。尽管基因表达谱已经发现了组成这一实体的分子亚群，但人们对这些基因表达变化的机制知之甚少。到目前为止，一些研究已经探索了突变在DLBCL肿瘤中的作用。外显子捕获技术和高通量测序的出现为外显子范围内最有可能导致基因和蛋白质表达改变的突变的鉴定提供了新的机会。通过溶液外显子捕获，我们的目标是对至少10%的患者中发生的临床相关突变进行外显子范围的筛查。我们坚信，这项研究将揭示疾病生物学的新方面和潜在的治疗靶点。 公共卫生相关性：我们的工作将有助于更好地了解淋巴瘤的遗传基础，并有助于开发更好的淋巴瘤治疗方法

DESCRIPTION (provided by applicant): Diffuse large B cell lymphoma (DLBCL) is the most common form of lymphoma and accounts for nearly 40% of all cases of non Hodgkin lymphoma. The disease exhibits a striking clinical heterogeneity. Less than half of the patients are cured with standard multi-agent chemotherapy. On the other hand, over half the patients experience early progression, relapse and death from the disease, when treated with the same regimen. The chemotherapy regimens used in the disease have changed little for nearly 30 years. Although gene expression profiling has uncovered molecular subgroups that comprise this entity, little is known about mechanisms underlying these changes in gene expression. Thus far, a handful of studies have explored the role of mutations in DLBCL tumors. The advent of exon-capture technologies and high throughput sequencing provide new opportunities for the exome-wide identification of mutations that are most likely to result in altered gene and protein expression. Through in-solution exon-capture, we aim to perform an exome-wide screen for clinically relevant mutations that occur in at least 10% of patients. We strongly believe that this study will reveal new aspects of disease biology and potential therapeutic targets. PUBLIC HEALTH RELEVANCE: Our work will allow a better understanding of the genetic basis of lymphomas and enable the development of better treatments in lymphoma