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Article

A glycolytic metabolite bypasses "two-hit" tumor suppression by BRCA2.

Cell - 25 Apr 2024

Kong Li Ren, Gupta Komal, Wu Andy Jialun, Perera David, Ivanyi-Nagy Roland, Ahmed Syed Moiz, Tan Tuan Zea, Tan Shawn Lu-Wen, Fuddin Alessandra, Sundaramoorthy Elayanambi, Goh Grace Shiqing, Wong Regina Tong Xin, Costa Ana S H, Oddy Callum, Wong Hannan, Patro C Pawan K, Kho Yun Suen, Huang Xiao Zi, Choo Joan, Shehata Mona, Lee Soo Chin, Goh Boon Cher, Frezza Christian, Pitt Jason J, Venkitaraman Ashok R

Abstract excerpt

Knudson's "two-hit" paradigm posits that carcinogenesis requires inactivation of both copies of an autosomal tumor suppressor gene. Here, we report that the glycolytic metabolite methylglyoxal (MGO) transiently bypasses Knudson's paradigm by inactivating the breast cancer suppressor protein BRCA2 to elicit a cancer-associated, mutational single-base substitution (SBS) signature in nonmalignant mammary cells or...

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Methodology Data sources Editorial policy Privacy About Contact Helena Bioinformatics

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Identifiers

PMID: 38608703
DOI: 10.1016/j.cell.2024.03.006

Provenance

PubMed metadata and Literature Corpus relationships. Corpus snapshot updated 7 Sept 2026. Manifest publication-graph-cohort-2026-09-07.1.

Source receipt: pubmed, retrieved 7 Sept 2026.

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