Lack of large genomic deletions in BRIP1, PALB2, and FANCD2 genes in BRCA1/2 negative familial breast cancer.

摘要: 16% of the familial BC cases [2]. Other sus-ceptibility genes include TP53 [16], PTEN [15], ATM [24],LKB1/STK11 [8], CHEK2 [28], BRIP1/FANCJ [27], andPALB2/FANCN [22]. However to date, majority offamilial can not be attributed mutations in oneof known susceptibility genes.The discovery breast cancer geneBRCA2asthegenedefectiveintheFanconianemia(FA)-D1complementation group [11], identification BRIP1(BRCA1 InteractingProtein)[3, 12,13] andPALB2 (PartnerAnd Localizer BRCA2) [23, 32] as responsiblefor FA-J and FA-N complementation groups, respec-tively, established a clear link between FA. Fanconi anemia (FA) is recessivelyinherited chromosomal instability syndrome with autosomalor X-linked mode inheritance, characterized by anincreased several forms malignancies [1,17].Thediseaseiscausedbymutationsinoneofthe13genesso far identified [18]. The FA gene products interact acommon pathway whereby most proteins (FANCA, -B, -C, -E, -F, -G, -L, -M) form multiprotein complexthat required for monoubiquitination FANCD2 andFANCI.However,thismodificationstepisnotinfluencedbyFANCD1(BRCA2),FANCJ(BRIP1),orFANCN(PALB2),and hence these seem act downstream thisprocess. FANCI are thought proteincomplex (ID complex), which translocates DNA damagesites where it co-localizes proteins,BRCA2/FANCD1, BRIP1/FANCJ, PALB2/FANCNand other that involved recognition andrepair damage, such BRCA1, ATM, NBS, andRAD51 [31].Several studies explored whether heterozygous femalecarriers mutation one atincreased risk cancer. To only inthe ‘‘downstream’’ have been found signifi-cantly elevate developing Het-erozygous PALB2/FANCNappear increase 2- 2.3-fold, respectively [22,27]. Risk assessment has based on screening fortruncating breastcancer (FBC) patients lacking BRCA1/2.Furthermore, mutations, suggested toplay role development onobservations Fancd2 knockout mice, demon-strated high incidence epithelial tumors, includingmammary ovarian tumors [10]. However, humans asignificant contribution FBCcould [14, 26].