1. Immune infiltration, aggressive pathology, and poor survival outcomes in RECQL helicase deficient breast cancers.
- Author
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Lashen A, Al-Kawaz A, Jeyapalan JN, Alqahtani S, Shoqafi A, Algethami M, Toss M, Green AR, Mongan NP, Sharma S, Akbari MR, Rakha EA, and Madhusudan S
- Subjects
- Humans, Female, RecQ Helicases genetics, Genetic Predisposition to Disease, Biomarkers, Tumor genetics, Forkhead Transcription Factors genetics, Breast Neoplasms pathology, Carcinoma, Intraductal, Noninfiltrating pathology
- Abstract
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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)
- Published
- 2024
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