Multifocal ileal NETs study WGS HFG3FCCXY

Ileal neuroendocrine tumors (NETs) represent the most common neoplasm of the small intestine. Although up to 50% of patients with ileal NETs are diagnosed with multifocal disease, the mechanisms by which multifocal ileal NETs arise are not yet understood. In this study, we analyzed genome-wide sequencing data to examine patterns of copy number variation in 40 synchronous primary ileal NETs derived from three patients. Chromosome (chr) 18 loss of heterozygosity (LOH) was the most frequent copy number alteration identified; however, not all primary tumors from the same patient had evidence of this LOH. Our data revealed three distinct patterns of chr18 allelic loss, indicating that primary tumors from the same patient can present different LOH patterns including retention of either parental allele. In conclusion, our results are consistent with the model that multifocal ileal NETs originate independently. In addition, they suggest that there is no specific germline allele on chr18 that is the target of somatic LOH.EGA study EGAS00001005623

回肠神经内分泌肿瘤（ileal neuroendocrine tumors, NETs）是小肠最为常见的肿瘤性病变。尽管高达50%的回肠NETs患者被诊断为多灶性病变，但多灶性回肠NETs的发生机制目前仍未阐明。本研究对3名患者来源的40例同步原发性回肠NETs的全基因组测序数据进行分析，以探究其拷贝数变异模式。研究结果显示，18号染色体（chr18）杂合性缺失（loss of heterozygosity, LOH）是本次研究检出的最常见拷贝数改变；然而，同一患者的不同原发肿瘤并非均存在该LOH特征。本研究数据揭示了三种不同的chr18等位基因缺失模式，表明同一患者的原发肿瘤可呈现多样化的LOH模式，包括保留任意一种亲本等位基因。综上，本研究结果与多灶性回肠NETs独立起源的模型相一致。此外，研究结果提示，18号染色体上并不存在作为体细胞LOH靶点的特定生殖系等位基因。本研究数据集为EGA研究EGAS00001005623