RECQL is essential for genomic stability. Here, we evaluated RECQL in 449 pure ductal carcinomas in situ (DCIS), 152 DCIS components of mixed DCIS/invasive breast cancer (IBC) tumors, 157 IBC components of mixed DCIS/IBC and 50 normal epithelial terminal ductal lobular units (TDLUs). In 726 IBCs, CD8+, FOXP3+, IL17+, PDL1+, PD1+ T-cell infiltration (TILs) were investigated in RECQL deficient and proficient cancers. Tumor mutation burden (TMB) was evaluated in five RECQL germ-line mutation carriers with IBC by genome sequencing. Compared with normal epithelial cells, a striking reduction in nuclear RECQL in DCIS was evident with aggressive pathology and poor survival. In RECQL deficient IBCs, CD8+, FOXP3+, IL17+ or PDL1+ TILs were linked with aggressive pathology and shorter survival. In germline RECQL mutation carriers, increased TMB was observed in 4/5 tumors. We conclude that RECQL loss is an early event in breast cancer and promote immune cell infiltration.

RECQL 对于基因组稳定性至关重要。在这里，我们评估了 449 例纯导管原位癌( DCIS)、152 例混合性 DCIS/浸润性乳腺癌 (IBC) 肿瘤的 DCIS 成分、157 例混合性 DCIS/IBC 的 IBC 成分和 50 例正常上皮终末导管小叶单位 (TDLU) 的 RECQL 。在 726 个 IBC 中，对 RECQL 缺乏和充分的癌症中的 CD8+、FOXP3+、IL17+、PDL1+、PD1+ T 细胞浸润 (TIL) 进行了研究。通过基因组测序评估了 5 名患有 IBC的 RECQL种系突变携带者的肿瘤突变负荷 (TMB)。与正常上皮细胞相比，DCIS 中核 RECQL 显着降低，且具有侵袭性病理和较差的生存率。在 RECQL 缺陷的 IBC 中，CD8+、FOXP3+、IL17+ 或 PDL1+ TIL 与侵袭性病理和较短的生存期相关。在种系RECQL突变携带者中，4/5 的肿瘤中观察到 TMB 增加。我们得出结论，RECQL 丢失是乳腺癌的早期事件，并促进免疫细胞浸润。