The Genetic Study of Families with a High Frequency of Hematopoietic Malignancy

层级摘要 霍奇金淋巴瘤(HL)和B前体急性淋巴细胞白血病(B-ALL)常见 儿童时期的恶性肿瘤，有很好的家族聚集性证据。这是一家人 聚集性可以用DNA的变化来解释，这种变化可能导致可以传播的疾病 代代相传。然而，到目前为止，人们对哪些基因突变知之甚少 基因导致HL或B-都是家族内的。为了更好地识别这些基因，我们有 对最大的一组家系进行全基因组测序(WGS) HL或B-ALL的发生频率。拥有来自受影响和未受影响的WGS信息 家族成员提高了发现这些重要疾病的潜在遗传基础的可能性 儿童家庭中的儿科癌症。我们对WGS结果的初步分析有 确定了潜在的感兴趣的基因，但需要进行广泛的分析来询问编码 区域、非编码区、拷贝数变体和结构变体。所有来自我们的调查结果 然后，将对这些疾病的零星队列患者的家庭进行频率验证。 已经执行了WG，并且他们的数据可用于分析。这项研究 很重要，因为它提供了一种创新和全面的方法来回答 是什么使患者易患HL和B-ALL的问题。《知识》 通过这项研究获得的信息将是无价的，因为它将帮助我们了解疾病的起源 并确定对HL和B-ALL患者进行更好的筛查、预防和治疗。

Lay Summary Hodgkin Lymphoma (HL) and B precursor acute lymphoblastic leukemia (B-ALL) are common malignancies of childhood with well documented evidence of familial clustering. This familial clustering may be explained by changes in DNA which may lead to diseases that can be passed from generation to generation. However, to date little is known regarding which mutations in genes are causing HL or B-ALL within families. To better identify these genes, we have performed whole genome sequencing (WGS) on the largest group of families with a high frequency of HL or B-ALL. Having this WGS information from both affected and unaffected family members improves the possibility of finding a potential genetic basis of these important pediatric cancers of childhood within the families. Preliminary analyses of our WGS results have identified potential genes of interest, but extensive analysis is needed to interrogate coding regions, non-coding regions, copy number variants and structural variants. All findings from our families will then be validated for frequency in a sporadic cohort of patients with these diseases that have already have WGS performed and their data are available for analyses. This research is important because it provides an innovative and comprehensive approach to answering the question of what predisposes patients to the development of HL and B-ALL. The knowledge gained through this study will be invaluable as it will help us understand the origin of the disease and identify better screening, prevention and treatment for patients with HL and B-ALL.