Immune infiltration, aggressive pathology, and poor survival outcomes in RECQL helicase deficient breast cancers

Neoplasia. 2023 Dec 21;47:100957. doi: 10.1016/j.neo.2023.100957. Online ahead of print.ABSTRACTRECQL 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.PMID:38134458 | DOI:10.1016/j.neo.2023.100957

Source: Neoplasia - December 22, 2023 Category: Cancer & Oncology Authors: Ayat Lashen Abdulbaqi Al-Kawaz Jennie N Jeyapalan Shatha Alqahtani Ahmed Shoqafi Mashael Algethami Michael Toss Andrew R Green Nigel P Mongan Sudha Sharma Mohammad R Akbari Emad A Rakha Srinivasan Madhusudan Source Type: research