E-resources
Peer reviewed
Open access
-
Pulver, Emilia M; Mukherjee, Chirantani; van de Kamp, Gerarda; Roobol, Stefan J; Rother, Magdalena B; van der Gulden, Hanneke; de Bruijn, Roebi; Lattanzio, Maria Valeria; van der Burg, Eline; Drenth, Anne Paulien; Verkaik, Nicole S; Hahn, Kerstin; Klarenbeek, Sjoerd; de Korte-Grimmerink, Renske; van de Ven, Marieke; Pritchard, Colin E J; Huijbers, Ivo J; Xia, Bing; van Gent, Dik C; Essers, Jeroen; van Attikum, Haico; Ray Chaudhuri, Arnab; Bouwman, Peter; Jonkers, Jos
Cancer research (Chicago, Ill.), 12/2021, Volume: 81, Issue: 24Journal Article
The tumor suppressor gene encodes a multidomain protein for which several functions have been described. These include a key role in homologous recombination repair (HRR) of DNA double-strand breaks, which is shared with two other high-risk hereditary breast cancer suppressors, BRCA2 and PALB2. Although both BRCA1 and BRCA2 interact with PALB2, missense variants affecting its PALB2-interacting coiled-coil domain are considered variants of uncertain clinical significance (VUS). Using genetically engineered mice, we show here that a BRCA1 coiled-coil domain VUS, p.L1363P, disrupts the interaction with PALB2 and leads to embryonic lethality. p.L1363P led to a similar acceleration in the development of -deficient mammary tumors as loss, but the tumors showed distinct histopathologic features, with more stable DNA copy number profiles in p.L1363P tumors. Nevertheless, p.L1363P mammary tumors were HRR incompetent and responsive to cisplatin and PARP inhibition. Overall, these results provide the first direct evidence that a BRCA1 missense variant outside of the RING and BRCT domains increases the risk of breast cancer. SIGNIFICANCE: These findings reveal the importance of a patient-derived BRCA1 coiled-coil domain sequence variant in embryonic development, mammary tumor suppression, and therapy response. .
Author
![loading ... loading ...](themes/default/img/ajax-loading.gif)
Shelf entry
Permalink
- URL:
Impact factor
Access to the JCR database is permitted only to users from Slovenia. Your current IP address is not on the list of IP addresses with access permission, and authentication with the relevant AAI accout is required.
Year | Impact factor | Edition | Category | Classification | ||||
---|---|---|---|---|---|---|---|---|
JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
Select the library membership card:
If the library membership card is not in the list,
add a new one.
DRS, in which the journal is indexed
Database name | Field | Year |
---|
Links to authors' personal bibliographies | Links to information on researchers in the SICRIS system |
---|
Source: Personal bibliographies
and: SICRIS
The material is available in full text. If you wish to order the material anyway, click the Continue button.