The BRCA1-PALB2-BRCA2 axis

or the BRCA pathway

plays key roles in genome stability maintenance and suppression of breast and several other cancers. Due to frequent p53 mutations in human

BRCA1

breast cancers and mouse mammary tumors from

Brca1

Brca2

and

Palb2

conditional knockout models

it is often thought that p53 inactivation accelerates BRCA1/2 and PALB2-associated tumorigenesis. Here

we studied tumor development in mice with a mutation in

Palb2

that disengages the PALB2-BRCA1 interaction in different

Trp53

backgrounds. Rather than mammary tumors

Palb2

and

Trp53

compound mutant mice developed

with greatly reduced latencies

lymphomas and sarcomas that are typically associated with germline

Trp53

inactivation. Whole exome sequencing failed to identify any significant differences in genomic features between the same tumor types of

Trp53

single mutant and

Palb2;Trp53

compound mutant mice. These results suggest that loss of the BRCA pathway accelerates p53-associated tumor development

possibly without altering the fundamental tumorigenic processes.