biorxiv.org· Toong, P. J., Boushaki, S., Zhao, S. J., Brough, R., Song, F. F., Krastev, D. B., Black, D., Rinaldi, G., Badja, C., Degasperi, A., Czarnecki, J., Memari, Y., Davies, H., Huebschmann, D., Glimm, H., Froehling, S., Tutt, A. N. J., Pettitt, S., Lord, C. J., Koh, G. C., Nik-Zainal, S. ·· 1 day agoScore67
Global signatures of Ribonucleotide Excision Repair deficiency and its therapeutic vulnerabilities
Global signatures of Ribonucleotide Excision Repair deficiency and its therapeutic vulnerabilities
In brief
Ribonucleotide excision repair (RER) deficiency produces a distinct genome-wide mutational phenotype, and a new whole-genome classifier, RERDetect, detects RER-deficient tumors across cancer types. Applied to more than 11,000 primary and metastatic cancers, it found a recurrent subset of RER-deficient tumors, most lacking detectable RNASEH2 genetic alterations, with RNASEH2C promoter hypermethylation as a recurrent inactivation mechanism. RER-deficient cells were sensitive to EXO1 and FANCM inhibition, making RER deficiency a therapeutically actionable repair-deficient state.
Source: biorxiv.org · biorxiv.org