Other

Dataset Information

0

A BRCA1 coiled-coil domain variant disrupting PALB2 interaction predisposes to mammary tumors with a targetable defect in homologous recombination repair [CNV-seq]


ABSTRACT: The BRCA1 tumor suppressor gene encodes a multi-domain protein for which several functions have been described. These include a key role in homologous recombination repair (HRR) of DNA double-strand breaks (DSBs), which is shared with two other high-risk hereditary breast cancer suppressors, BRCA2 and PALB2. Although both BRCA1 and BRCA2 interact with PALB2, BRCA1 missense variants affecting its PALB2-interacting coiled-coil domain are considered sequence variants of uncertain clinical significance (VUS). Using genetically engineered mice, we now show that a BRCA1 coiled-coil domain VUS, Brca1 p.L1363P, disrupting the interaction with PALB2 leads to embryonic lethality and loss of breast cancer suppression. Brca1 p.L1363P mammary tumors develop with a similar latency as Brca1-null tumors, but show different histopathological features and more stable DNA copy number profiles. Nevertheless, Brca1 p.L1363P mammary tumors are HRR-incompetent and responsive to cisplatin and PARP inhibition.

ORGANISM(S): Mus musculus

PROVIDER: GSE182449 | GEO | 2022/02/01

REPOSITORIES: GEO

Dataset's files

Source:
Action DRS
Other
Items per page:
1 - 1 of 1

Similar Datasets

2022-02-01 | GSE182448 | GEO
| PRJNA756277 | ENA
| PRJNA756282 | ENA
| PRJNA756281 | ENA
2011-10-11 | E-GEOD-32896 | biostudies-arrayexpress
2011-01-21 | E-GEOD-26723 | biostudies-arrayexpress
2011-10-12 | GSE32896 | GEO
2011-01-21 | GSE26723 | GEO
2023-10-13 | GSE237142 | GEO
2022-08-06 | GSE210602 | GEO