Carolina Guerrero

The University of Texas MD Anderson Cancer Center

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Trends

Author Order

Document Type

Co-Authors

Martina Ott

The University of Texas MD Anderson Cancer Center

Poojan Shukla

University of California, San Francisco

Yue Chen

Fuzhou University

Xiaogang Wu

Peking University

Detlev Schindler

University of Würzburg

Courtney D. DiNardo

The University of Texas MD Anderson Cancer Center

Karl-Heinz Tomaszowski

The University of Texas MD Anderson Cancer Center

Katharina Schlacher

The University of Texas MD Anderson Cancer Center

Sunetra Roy

The University of Texas MD Anderson Cancer Center

Caezaan Keshvani

The University of Texas MD Anderson Cancer Center

Cooperative Institutions

The University of Texas MD Anderson Cancer Center

The University of Texas Health Science Center at Houston

Neurological Surgery

Miltenyi Biotec (Germany)

German Cancer Research Center

Heidelberg University

Immatics Biotechnologies (Germany)

Universitätsmedizin Göttingen

University of Göttingen

Baylor College of Medicine

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Field

Hypomorphic Brca2 and Rad51c double mutant mice display Fanconi anemia, cancer and polygenic replication stress

Nature Communications (2023)

Karl-Heinz Tomaszowski Sunetra Roy Carolina Guerrero Poojan Shukla Caezaan Keshvani

Abstract The prototypic cancer-predisposition disease Fanconi Anemia (FA) is identified by biallelic mutations in any one of twenty-three FANC genes. Puzzlingly, inactivation of one Fanc gene alone in mice fails to faithfully model the pleiotropic human disease without additional external stress. Here we find that FA patients frequently display FANC co-mutations. Combining exemplary homozygous hypomorphic Brca2/Fancd1 and Rad51c/Fanco mutations in mice phenocopies human FA with bone marrow failure, rapid death by cancer, cellular cancer-drug hypersensitivity and severe replication instability. These grave phenotypes contrast the unremarkable phenotypes seen in mice with single gene-function inactivation, revealing an unexpected synergism between Fanc mutations. Beyond FA, breast cancer-genome analysis confirms that polygenic FANC tumor-mutations correlate with lower survival, expanding our understanding of FANC genes beyond an epistatic FA-pathway. Collectively, the data establish a polygenic replication stress concept as a testable principle, whereby co-occurrence of a distinct second gene mutation amplifies and drives endogenous replication stress, genome instability and disease.

10.1038/s41467-023-36933-y

Cite

Citations (5)

Author Correction: Hypomorphic Brca2 and Rad51c double mutant mice display Fanconi anemia, cancer and polygenic replication stress

Nature Communications (2024)

Karl-Heinz Tomaszowski Sunetra Roy Carolina Guerrero Poojan Shukla Caezaan Keshvani

Replication

10.1038/s41467-024-46561-9

Cite

Citations (0)