We show that a SNP near the CTSO gene is a poor prognostic factor in breast cancer although further research might help to reveal the factors linking this genotype and prognosis.
Our data show that HER2 mutations are rare in HER2-positive Japanese breast cancer patients. The two mutations found in this study were identical, S310F. We suggest that in vitro experiments to determine whether the S310F mutation could be involved in resistance to anti-HER2 drugs are worthwhile in future.
Background : Inositol polyphosphate 5-phosphatase PIPP (INPP5J) has been identified as a suppressor of oncogenic PI3K/Akt signaling in breast cancer.INPP5J depletion increases transformation and accelerates oncogene-driven tumor growth in vivo, while paradoxically reducing cell migration, invasion, and metastasis. Therefore, we hypothesized that INPP5J gene expression in human breast cancer tissues would be prognostic in early breast cancer patients over long-term follow-up. Methods: A total of 478 breast cancer tissue samples collected between 2003 and 2008 was available for analysis. We measured INNPP5J mRNA using a TaqMan gene expression assay. PIK3CA mutation status was evaluated using a TaqMan mutation detection assay. We then investigated the correlations of clinicopathological factors and prognosis with levels of INPP5J mRNA and the PIK3CA mutation status. Results: INPP5J mRNA was expressed at a low level in 30.1% (144/478) and at a medium to high level in the remaining breast cancer samples. Low INPP5J mRNA correlated with larger tumor (p=0.015), high grade (p<0.0001) and, ER-negativity (p<0.0001). PIK3CA mutations were detected in 46% (63/138) of patients analyzed. We found that disease-free survival (DFS) was significantly worse in patients with low levels of INPP5J (p=0.008). Although DFS and INPP5J levels tended to be associated in estrogen receptor (ER)-positive patients (p=0.052), DFS was significantly worse in patients with wild-type PIK3CA and low INPP5J mRNA expression (p=0.008). Conclusion: We shows that the level of INPP5J mRNA expression is prognostics in breast cancer patients and that its prognostic impact is affected by PIK3CA mutation status. Citation Format: Kondo N, Kim T-S, Wanifuchi Y, Hato Y, Hisada T, Nishimoto M, Nishikawa S, Toyama T. The prognostic impact of inositol polyphosphate 5-phosphatase PIPP (INPP5J) expression in breast cancer tissue [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-07-34.
Background: Although taxanes are a mainstay of breast cancer treatment, some cases are resistant to these drugs. This is a crucial issue in breast cancer therapy. In the emerging era of next-generation sequencing, it is possible to obtain extensive genomic information on individual tumors in a very short time. Using this technology, it was reported that specific mutations might affect therapeutic efficacy and induce resistance to specific treatment. Objective: The aim of this study was to investigate the mechanisms of taxane resistance using whole exon sequencing and expression analyses in human breast cancer tissues. Materials and Methods: We selected six breast cancer patients whose tumors responded well to anthracycline treatment but suffered disease progression on taxane treatment. We then performed whole exon sequencing on these samples using HiSeq (Illumia). In this way, we identified somatic mutations of candidate genes considered to be instrumental for mediating resistance to taxanes. Next, we performed mRNA expression analyses of these candidate genes in a further 122 breast cancers treated with taxanes at our institute. Finally, we correlated mRNA expression levels of these genes with clinicopathological factors and prognosis. Results: We identified 9 mutations common to all 6 patients analyzed in this study, and a further 16 mutations shared by 5 of them. Kaplan-Meier analyses showed that high level mRNA expression of 3 of these 25 genes was significantly associated with poorer disease-free survival. Moreover, high level mRNA expression of one of these three genes was significantly associated with worse overall survival. However, there were no significant correlations between expression levels of these three genes and any clinicopathologeical features. Conclusion: Using next-generation sequencing, we have identified three candidate genes involved in resistance to taxane treatment in breast cancer. We are now analyzing the functional attributes of these three genes. Citation Format: Endo Y, Dong Y, Kondo N, Hato Y, Hisada T, Nishimoto M, Nishikawa S, Takahashi S, Toyama T. Exome sequencing of human breast cancer tissues resistant to taxanes [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-03-07.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.