The genetic predisposition to lymphoma is not fully understood. We identified 13 lymphoma‐cancer families (2011–2021), in which 27 individuals developed lymphomas and 26 individuals had cancers. Notably, male is the predominant gender in lymphoma patients, whereas female is the predominant gender in cancer patients (p = .019; OR = 4.72, 95% CI, 1.30–14.33). We collected samples from 18 lymphoma patients, and detected germline variants through exome sequencing. We found that germline protein truncating variants (PTVs) were enriched in DNA repair and immune genes. Totally, we identified 31 heterozygous germline mutations (including 12 PTVs) of 25 DNA repair genes and 19 heterozygous germline variants (including 7 PTVs) of 14 immune genes. PTVs of ATM and PNKP were found in two families, respectively. We performed whole genome sequencing of diffuse large B cell lymphomas (DLBCLs), translocations at IGH locus and activation of oncogenes (BCL6 and MYC) were verified, and homologous recombination deficiency was detected. In DLBCLs with germline PTVs of ATM, deletion and insertion in CD58 were further revealed. Thus, in lymphoma‐cancer families, we identified germline defects of both DNA repair and immune genes in lymphoma patients.

中文翻译：

---

淋巴瘤-癌症家族淋巴瘤中 DNA 修复和免疫基因的种系变异

淋巴瘤的遗传倾向尚不完全清楚。我们确定了 13 个淋巴瘤-癌症家族（2011 年至 2021 年），其中 27 人患有淋巴瘤，26 人患有癌症。值得注意的是，男性是淋巴瘤患者的主要性别，而女性是癌症患者的主要性别。p= .019；OR = 4.72，95% CI，1.30–14.33）。我们收集了 18 名淋巴瘤患者的样本，并通过外显子组测序检测了种系变异。我们发现种系蛋白截短变体 (PTV) 富含 DNA 修复和免疫基因。总共，我们鉴定了 25 个 DNA 修复基因的 31 个杂合种系突变（包括 12 个 PTV）和 14 个免疫基因的 19 个杂合种系变异（包括 7 个 PTV）。PTV 的自动提款机和PNKP分别在两个家庭中被发现。我们对弥漫性大 B 细胞淋巴瘤 (DLBCL)、IGH 基因座易位和癌基因激活进行了全基因组测序（BCL6和我的C）进行了验证，并检测到同源重组缺陷。在具有种系 PTV 的 DLBCL 中自动提款机，删除和插入CD58被进一步揭晓。因此，在淋巴瘤-癌症家族中，我们发现了淋巴瘤患者 DNA 修复和免疫基因的种系缺陷。