The major processes in carcinogenesis include the inactivation of tumor-suppressor genes (TSGs). Although Knudson's two-hit model requires two independent inactivating mutations, perhaps more frequently, a TSG inactivation can occur through a loss of heterozygosity (LOH) of an inactivating mutation. Deletion and uniparental disomy (UPD) have been well documented as LOH mechanisms, but the role of gene conversion is poorly understood. Here, we developed a simple algorithm to detect somatic gene conversion from short-read sequencing data. We applied it to 6285 cancer patient samples, from which 4978 somatic mutations that underwent gene conversion to achieve LOH were found. This number accounted for 14.8% of the total LOH mutations. We further showed that LOH by gene conversion was enriched in TSGs compared with non-TSG genes, showing a significant contribution of gene conversion to carcinogenesis.

中文翻译：

---

频繁的体细胞基因转换作为肿瘤抑制基因杂合性丢失的机制

致癌作用的主要过程包括肿瘤抑制基因 (TSG) 的失活。尽管 Knudson 的两次打击模型需要两个独立的失活突变，但可能更频繁地发生 TSG 失活可能是通过失活突变的杂合性 (LOH) 丢失而发生的。缺失和单亲二体性 (UPD) 已被详细记录为 LOH 机制，但人们对基因转换的作用知之甚少。在这里，我们开发了一种简单的算法来检测短读长测序数据中的体细胞基因转换。我们将其应用于 6285 个癌症患者样本，从中发现了 4978 个经历基因转换以实现 LOH 的体细胞突变。这个数字占总 LOH 突变的 14.8%。我们进一步表明，与非 TSG 基因相比，通过基因转换产生的 LOH 在 TSG 中更丰富，