DESCRIPTION:

Real-time PCR arrays were used to compare expression levels of 120 DNA repair related genes in 43 pretreatment biopsies of BRCA1-associated TNBCs exhibiting pathologic complete response or non-pathological responses after neoadjuvant chemotherapy with cisplatin. Genes were recorded using HGNC identifiers. Values represent fold-change of downregulation.

LABEL:

downregulated in BRCA1 TNBC showing complete pathological response

SCORE TYPE:

Effect

DATE ADDED:

2017-04-24

DATE UPDATED:

2024-04-25

SPECIES:

AUTHORS:

Domagala P, Hybiak J, Rys J, Byrski T, Cybulski C, Lubinski J

TITLE:

Pathological complete response after cisplatin neoadjuvant therapy is associated with the downregulation of DNA repair genes in BRCA1-associated triple-negative breast cancers.

JOURNAL:

Oncotarget Oct 2016, Vol 7, pp. 68662-68673

ABSTRACT:

Pathologic complete response (pCR) after neoadjuvant chemotherapy is considered a suitable surrogate marker of treatment efficacy in patients with triple-negative breast cancers (TNBCs). However, the molecular mechanisms underlying pCR as a result of such treatment remain obscure. Using real-time PCR arrays we compared the expression levels of 120 genes involved in the main mechanisms of DNA repair in 43 pretreatment biopsies of BRCA1-associated TNBCs exhibiting pCR and no pathological complete response (non-pCR) after neoadjuvant chemotherapy with cisplatin. Altogether, 25 genes were significantly differentially expressed between tumors exhibiting pCR and non-pCR, and these genes were downregulated in the pCR group compared to the non-pCR group. A difference in expression level greater than 1.5-fold was detected for nine genes: MGMT, ERCC4, FANCB, UBA1, XRCC5, XPA, XPC, PARP3, and RPA1. The non-homologous end joining and nucleotide excision repair pathways of DNA repair showed the most significant relevance. Expression profile of DNA repair genes associated with pCR was different in the node-positive (20 genes with fold change >1.5) and node-negative (only 3 genes) subgroups. Although BRCA1 germline mutations are the principal defects in BRCA1-associated TNBC, our results indicate that the additional downregulation of other genes engaged in major pathways of DNA repair may play a decisive role in the pathological response of these tumors to cisplatin neoadjuvant chemotherapy. The results suggest that patients with node-positive BRCA1-associated TNBCs that do not exhibit pCR after cisplatin neoadjuvant chemotherapy may be candidates for subsequent therapy with PARP inhibitors, whereas UBA1 may be a potential therapeutic target in node-negative subgroup. PUBMED: 27626685
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