Exome-wide screening for common mutations in lymphoma

描述（由申请人提供）：弥漫性大B细胞淋巴瘤（DLBCL）是最常见的淋巴瘤，占所有非霍奇金淋巴瘤病例的近40%。这种疾病表现出明显的临床异质性。不到一半的患者通过标准的多药化疗治愈。另一方面，当采用相同的治疗方案时，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，用于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揭示了构成这一实体的分子亚群，但对这些基因表达变化的机制知之甚少。到目前为止，少数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的突变鉴定提供了新的机会，这些突变最有可能导致基因和蛋白质表达的改变。通过溶液内外显子捕获，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全组筛选。我们坚信这项研究将揭示疾病生物学和潜在治疗靶点的新方面。

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