cerevisiae) ID2 inhibitor of DNA binding 2, dominant negative helix-loop-helix protein TOR1A torsin family 1, member A (torsin A) PTPRK protein tyrosine phosphatase, receptor type, K SESN1 sestrin 1 TXLNA taxilin alpha DCK deoxycytidine kinase RSU1 Ras suppressor protein 1 MTF2 metal response element binding transcription factor 2 SPAG7 sperm associated antigen 7 NCOA3
nuclear receptor coactivator 3 GFPT1 glutamine-fructose-6-phosphate transaminase 1 MBNL1 muscleblind-like (Drosophila) PIK3R3 phosphoinositide-3-kinase, regulatory subunit 3 (gamma) NPC1 Niemann-Pick disease, type C1 ANO10 anoctamin 10 CDK7 cyclin-dependent kinase 7 B Gene Symbol Gene Title ELAC2 elaC homolog 2 (E.
Ligand-activated PPARs interact with coactivators CEBPA/B and NCOA3
and in the unliganded state with corepressor NCOR2 [4-7].
is a selective co-activator of estrogen receptor [alpha]-mediated transactivation of PLAC1 in MCF-7 breast cancer cells," BMC Cancer, vol.
Seven SNP loci from 5 genes, ESR1, estrogen receptor 2 (ESR2), nuclear receptor coactivator 3 (NCOA3), peroxisome proliferator-activated receptor gamma, coactivator 1 beta (PPARGC1B), and related RAS viral (rras) oncogene homolog 2 (RRAS2, alias TC21) with different minor allele frequencies were genotyped (Table 1 and Table 2) by using MALDI-TOF mass spectrometry (MS) according to manufacturer's instructions (Sequenom MassARRAY platform).
Five genes related to breast cancer biology were selected to represent estrogen receptor signaling (ESR1, ESR2), estrogen receptor activation (NCOA3, PPARGC1B), or RAS/MAPK signal transduction (RRAS2).
The sample dropout rate in this investigation was <10% across all assays, which indicates that the automated extraction method provides genomic DNA of a quality comparable to that in similar studies in which archived FFPE tissue samples were used with manual DNA extraction procedures (5).We selected 5 genes known to harbor germline polymorphisms that have been reported to be related to breast cancer risk or disease progression (14,15), to functionally influence estrogen-receptor activity (NCOA3), or to be predictive for breast cancer tamoxifen outcome (16).
Tumors Gene location genotyped, n (%) ESR1 6q25.1 rs9340799 97 (92.3) ESR2 14q23.2 rs4986938 97 (92.3) ESR2 14q23.2 rs944052 101 (96.2) NCOA3 20q12 rs2230782 98 (93.3) NCOA3 20q12 rs2076546 98 (93.3) PPARGC1B 5q32 rs7732671 102 (97.1) RRAS2 11p15.2 rs11023197 96 (91.4) Normal tissues Tumor-normal Identical/total Gene genotyped, pairs, n chromosomes, n (%) n/N, (%) ESR1 101 (96.2) 94 187/188(99.4) ESR2 100 (95.2) 92 183/184(99.4) ESR2 102 (97.1) 98 194/196(98.9) NCOA3 101 (96.2) 95 189/190(99.5) NCOA3 101 (96.2) 95 188/190(98.9) PPARGC1B 103 (98.1) 100 198/200(99.0) RRAS2 99 (94.3) 91 181/182 (99.4) Table 2.
Two of the best-studied of these novel prognostic markers are osteopontin and nuclear receptor coactivator 3 (NCOA3).
The NCOA3 gene is located on a region of chromosome 20 that's often amplified in human breast cancer.
NCOA3 immunostaining was scored by a dermatopathologist blinded as to patient outcome.
The co-activator NCOA3
, also known as amplified in breast cancer-1 (AIB1) is overexpressed in 50% of breast cancers and amplified in 5% .
De esta manera se han encontrado amplificaciones en algunos de esos genes y se ha observado hasta el momento que su presencia en ciertas poblaciones podria estar contribuyendo a aumentar el riesgo a padecer: enfermedad bipolar cuando hay amplificacion en el gen SEF2-1B, OMIM 602272; autismo cuando estan en el gen RELN, OMIM 600514; sindrome de Jacobsen en el gen CBL2, OMIM 147791; cancer de ovarios en el gen hRAS1, OMIM 190020 y cancer de prostata en el gen NCOA3
, OMIM 601937 (Anonimo 2004).