直肠神经内分泌肿瘤（R-NETs）的遗传特征尚不明确。描绘遗传特征可为预后预测和新型治疗开发提供生物学基础。使用全外显子组测序分析了18名R-NET患者的组织。中位肿瘤突变负荷（TMB）和微卫星不稳定性（MSI）分别为1.15 Muts/MB（范围为0.03-23.28）和0.36（范围为0.00-10.97）。与P53信号通路、PI3K-AKT信号通路、DNA损伤修复、WNT信号通路等相关的基因经常发生改变。较高的TMB（p = 0.078）、较高的CNV（p = 0.110）、CCDC168的体细胞突变（p = 0.049）、HMCN1（p = 0.040）、MYO10（p = 0.007）的体细胞突变和ZC3H13扩增（p <0.001）与更短的OS相关。72％的患者中有可能靶向的基因突变（PTGA）。FGFR1扩增（22％）是最常见的PTGA，其次是BARD1和BRCA2基因突变（各为17％）。与免疫检查点阻断（ICB）疗效相关的基因变异中，常见的是FAT1变异（39％）和PTEN耗竭（28％）。总之，经常改变的致癌通路可能有助于R-NETs的发展和进展。与预后相关的基因突变可能是潜在的新型靶点。靶向治疗可能是一种有前途的策略，因为R-NETs中可靶向的突变很普遍。除了R-NETs总体低的TMB和MSI外，FAT1变异和PTEN耗竭可能是影响ICB反应的主要基因突变。

The genetic characteristics of rectal neuroendocrine tumors (R-NETs) were poorly understood. Depicting the genetic characteristics may provide a biological basis for prognosis prediction and novel treatment development. Tissues of 18 R-NET patients were analyzed using whole-exome sequencing. The median tumor mutation burden (TMB) and microsatellite instability (MSI) were 1.15 Muts/MB (range, 0.03-23.28) and 0.36 (range, 0.00-10.97) respectively. Genes involved in P53 signaling, PI3K-AKT signaling, DNA damage repair, WNT signaling, etc. were frequently altered. Higher TMB (P = 0.078), higher CNV (P = 0.110), somatic mutation of CCDC168 (P = 0.049), HMCN1 (P = 0.040), MYO10 (P = 0.007), and amplification of ZC3H13 (P < 0.001) were associated with shorter OS. Potentially targetable gene alterations (PTGAs) were seen in 72% of the patients. FGFR1 amplification (22%) was the most common PTGA followed by BARD1 and BRCA2 mutation (each 17%). As for gene variations associated with the efficacy of immune checkpoint blockade (ICB), FAT1 alteration (39%) and PTEN depletion (28%) were commonly observed. In conclusion, frequently altered oncogenic pathways might contribute to the development and progression of R-NETs. Gene alterations significantly associated with prognosis might be potential novel targets. Targeted therapy might be a promising strategy as targetable alterations were prevalent in R-NETs. FAT1 alteration and PTEN depletion might be the main genetic alterations influencing the response to ICB besides overall low TMB and MSI in R-NETs.