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https://www.readbyqxmd.com/read/28521409/evaluation-of-a-novel-approach-to-circulating-tumor-cell-isolation-for-cancer-gene-panel-analysis-in-patients-with-breast-cancer
#1
Soo Jeong Lee, Cham Han Lee, Sung Ho Choi, Sei Hyun Ahn, Byung Ho Son, Jong Won Lee, Jong Han Yu, Nak-Jung Kwon, Woo Chung Lee, Kap-Seok Yang, Dong Hyoung Lee, Du Yeol Han, Mi So Choi, Pyeong-Soo Park, Hyun Kyung Lee, Myoung Shin Kim, Jinseon Lee, Byung Hee Jeon
Liquid biopsy isolation of circulating tumor cells (CTCs) allows the genomic analysis of CTCs, which is useful in the determination of personalized cancer therapy. In the present study, CTCs from patients with breast cancer were enriched and successfully analyzed using cancer gene panel analysis. Blood samples from 11 patients with breast cancer were collected and CTCs enriched for using size-based filtration. The enriched CTCs were analyzed using immunofluorescence staining with antibodies directed against epithelial cell adhesion molecule (EpCAM) and cluster of differentiation 45...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28518139/mir-106b-and-mir-93-regulate-cell-progression-by-suppression-of-pten-via-pi3k-akt-pathway-in-breast-cancer
#2
Nana Li, Yuan Miao, Yujia Shan, Bing Liu, Yang Li, Lifen Zhao, Li Jia
Accumulating evidences have revealed that dysregulated microRNAs (miRNAs) involve in the tumorigenesis, progression and even lead to poor prognosis of various carcinomas, including breast cancer. MiRNA-106b-5p (miR-106b) and miRNA-93-5p (miR-93) levels were confirmed to be significantly upregulated in breast cancer clinical samples (n=36) and metastatic cell line (MDA-MB-231) compared with those in the paired adjacent tissues and normal breast epithelial cell line (MCF-10A). Moreover, further research stated that the capability of migration, invasion and proliferation changed along with the altered expression of miR-106b and miR-93 in breast cancer...
May 18, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28513612/insertion-of-alu-elements-at-a-pten-hotspot-in-cowden-syndrome
#3
Louise Crivelli, Virginie Bubien, Natalie Jones, Jennifer Chiron, Françoise Bonnet, Emmanuelle Barouk-Simonet, Patrice Couzigou, Nicolas Sevenet, Frédéric Caux, Michel Longy
Cowden syndrome (CS) is an inherited autosomal dominant disorder associated with germline pathogenic variants of the PTEN tumor suppressor gene. Its phenotypical expression is highly variable and the existence of patients with a CS suggestive phenotype without pathogenic PTEN variant may be related to genetic heterogeneity. In order to explore this hypothesis through the detection of potentially deleterious variants enabling us to identify a new candidate gene, we performed whole-exome sequencing (WES) in a series of 22 CS patients without detectable PTEN pathogenic variant using conventional methods for mutation screening...
May 17, 2017: European Journal of Human Genetics: EJHG
https://www.readbyqxmd.com/read/28512246/tumor-associated-macrophages-promote-malignant-progression-of-breast-phyllodes-tumors-by-inducing-myofibroblast-differentiation
#4
Yan Nie, Jia-Ning Chen, Di Huang, Yandan Yao, Jiewen Chen, Lin Ding, Jiayi Zeng, Shicheng Su, Xue Chao, Fengxi Su, Herui Yao, Hai Hu, Erwei Song
Myofibroblast differentiation plays an important role in the malignant progression of phyllodes tumor (PT), a fast-growing neoplasm derived from periductal stromal cells of the breast. Macrophages are frequently found in close proximity with myofibroblasts, but it is uncertain whether they are involved in the myofibroblast differentiation during PT progression. Here we show that increased density of tumor associated macrophage (TAM) correlates with malignant progression of PT. We found that TAM stimulated myofibroblast differentiation and promoted the proliferation and invasion of PT cells...
May 16, 2017: Cancer Research
https://www.readbyqxmd.com/read/28499822/activation-of-stat3-hif-1%C3%AE-hes-1-axis-promotes-trastuzumab-resistance-in-her2-overexpressing-breast-cancer-cells-via-down-regulation-of-pten
#5
Safiyeh Aghazadeh, Razieh Yazdanparast
BACKGROUND: Resistance to the HER2-targeted antibody trastuzumab remains to be a major clinical challenge in the treatment of HER2-positive breast cancer. Hyper-activation of SATA3 is proposed to be a predictive biomarker of trastuzumab resistance. However, the precise mechanism(s) remains poorly defined. Evidence is emerging that HIF-1α, a central downstream element of STAT3 pathway, serves a pivotal role in the complex signaling network with subsequent diverse cellular events. MATERIAL AND METHODS: We have established trastuzumab resistant SKBR3 cells (SKBR3-TR)...
May 9, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28486781/genomic-analysis-of-inherited-breast-cancer-among-palestinian-women-genetic-heterogeneity-and-a-founder-mutation-in-tp53
#6
Suhair Lolas Hamameh, Paul Renbaum, Lara Kamal, Dima Dweik, Mohammad Salahat, Tamara Jaraysa, Amal Abu Rayyan, Silvia Casadei, Jessica B Mandell, Suleyman Gulsuner, Ming K Lee, Tom Walsh, Mary-Claire King, Ephrat Levy-Lahad, Moein Kanaan
Breast cancer among Palestinian women has lower incidence than in Europe or North America, yet is very frequently familial. We studied genetic causes of this familial clustering in a consecutive hospital-based series of 875 Palestinian patients with invasive breast cancer, including 453 women with diagnosis by age 40, or with breast or ovarian cancer in a mother, sister, grandmother, or aunt ("discovery series"); and 422 women diagnosed after age 40 and with negative family history ("older-onset sporadic patient series")...
May 9, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28476234/clinical-implications-for-germline-pten-spectrum-disorders
#7
REVIEW
Joanne Ngeow, Kaitlin Sesock, Charis Eng
Patients with PTEN hamartoma tumor syndrome (PHTS) may present to a variety of different subspecialties with benign and malignant clinical features. They have increased lifetime risks of breast, endometrial, thyroid, renal, and colon cancers, as well as neurodevelopmental disorders such as autism spectrum disorder. Patients and affected family members can be offered gene-directed surveillance and management. Patients who are unaffected can be spared unnecessary investigations. With longitudinal follow-up, we are likely to identify other non-cancer manifestations associated with PHTS such as metabolic, immunologic, and neurologic features...
June 2017: Endocrinology and Metabolism Clinics of North America
https://www.readbyqxmd.com/read/28469388/significant-prognostic-features-and-patterns-of-somatic-tp53-mutations-in-human-cancers
#8
Wensheng Zhang, Andrea Edwards, Erik K Flemington, Kun Zhang
TP53 is the most frequently altered gene in human cancers. Numerous retrospective studies have related its mutation and abnormal p53 protein expression to poor patient survival. Nonetheless, the clinical significance of TP53 (p53) status has been a controversial issue. In this work, we aimed to characterize TP53 somatic mutations in tumor cells across multiple cancer types, primarily focusing on several less investigated features of the mutation spectra, and determine their prognostic implications. We performed an integrative study on the clinically annotated genomic data released by The Cancer Genome Atlas...
2017: Cancer Informatics
https://www.readbyqxmd.com/read/28423632/the-genetic-variants-in-the-pten-pi3k-akt-pathway-predict-susceptibility-and-ce-a-f-chemotherapy-response-to-breast-cancer-and-clinical-outcomes
#9
Xiang Li, Ruishan Zhang, Zhuangkai Liu, Shuang Li, Hong Xu
The PI3K/PTEN/AKT pathway play a critical role in balancing cell growth and death. Epidemiologic studies suggested that mutations of the PI3K/PTEN/AKT pathway genes are associated with cancer risk, yet no data are available for PTEN rs701848, PIK3CA rs2699887, and AKT1 rs2494752 polymorphism and breast cancer(BC) risk. A case-control study was performed in 920 BC patients and 908 healthy controls using the TaqMan assay method. Overall, individuals with PTEN rs701848 TC, CC and TC/CC genotypes showed significant increased BC risk (P=0...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28419251/evaluating-genetic-variants-associated-with-breast-cancer-risk-in-high-and-moderate-penetrance-genes-in-asians
#10
Mi-Ryung Han, Wei Zheng, Qiuyin Cai, Yu-Tang Gao, Ying Zheng, Manjeet K Bolla, Kyriaki Michailidou, Joe Dennis, Qin Wang, Alison M Dunning, Paul Brennan, Shou-Tung Chen, Ji-Yeob Choi, Mikael Hartman, Hidemi Ito, Artitaya Lophatananon, Keitaro Matsuo, Hui Miao, Kenneth Muir, Suleeporn Sangrajrang, Chen-Yang Shen, Soo Hwang Teo, Chiu-Chen Tseng, Anna H Wu, Cheng Har Yip, Daehee Kang, Yong-Bing Xiang, Douglas F Easton, Xiao-Ou Shu, Jirong Long
Over the past 20 years, high-penetrance pathogenic mutations in genes BRCA1, BRCA2, TP53, PTEN, STK11 and CDH1 and moderate-penetrance mutations in genes CHEK2, ATM, BRIP1, PALB2, RAD51C, RAD50 and NBN have been identified for breast cancer. In this study, we investigated whether there are additional variants in these 13 genes associated with breast cancer among women of Asian ancestry. We analyzed up to 654 single nucleotide polymorphisms (SNPs) from 6269 cases and 6624 controls of Asian descent included in the Breast Cancer Association Consortium (BCAC), and up to 236 SNPs from 5794 cases and 5529 controls included in the Shanghai Breast Cancer Genetics Study (SBCGS)...
May 1, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28418444/associations-between-cancer-predisposition-testing-panel-genes-and-breast-cancer
#11
Fergus J Couch, Hermela Shimelis, Chunling Hu, Steven N Hart, Eric C Polley, Jie Na, Emily Hallberg, Raymond Moore, Abigail Thomas, Jenna Lilyquist, Bingjian Feng, Rachel McFarland, Tina Pesaran, Robert Huether, Holly LaDuca, Elizabeth C Chao, David E Goldgar, Jill S Dolinsky
Importance: Germline pathogenic variants in BRCA1 and BRCA2 predispose to an increased lifetime risk of breast cancer. However, the relevance of germline variants in other genes from multigene hereditary cancer testing panels is not well defined. Objective: To determine the risks of breast cancer associated with germline variants in cancer predisposition genes. Design, Setting, and Participants: A study population of 65 057 patients with breast cancer receiving germline genetic testing of cancer predisposition genes with hereditary cancer multigene panels...
April 13, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28416949/circulating-tumor-dna-in-a-breast-cancer-patient-s-plasma-represents-driver-alterations-in-the-tumor-tissue
#12
Jieun Lee, Sung-Min Cho, Min Sung Kim, Sug Hyung Lee, Yeun-Jun Chung, Seung-Hyun Jung
Tumor tissues from biopsies or surgery are major sources for the next generation sequencing (NGS) study, but these procedures are invasive and have limitation to overcome intratumor heterogeneity. Recent studies have shown that driver alterations in tumor tissues can be detected by liquid biopsy which is a less invasive technique capable of both capturing the tumor heterogeneity and overcoming the difficulty in tissue sampling. However, it is still unclear whether the driver alterations in liquid biopsy can be detected by targeted NGS and how those related to the tissue biopsy...
March 2017: Genomics & Informatics
https://www.readbyqxmd.com/read/28410191/loss-of-pten-expression-in-breast-cancer-association-with-clinicopathological-characteristics-and-prognosis
#13
Shuting Li, Yanwei Shen, Mengying Wang, Jiao Yang, Meng Lv, Pan Li, Zheling Chen, Jin Yang
Various studies have evaluated the significance of PTEN (phosphatase and tensin homolog deleted from chromosome 10) expression in breast cancer, but their results remain controversial. We conducted a meta-analysis to evaluate the associations of PTEN expression with clinicopathological characteristics and prognosis in breast cancer. PubMed, Embase, Web of Science, and China National Knowledge Infrastructure were searched to identify relevant publications. The associations between PTEN expression and clinicopathological parameters, disease-free survival (DFS), and overall survival (OS) were then assessed via meta-analyses of odds ratio (ORs) and hazard ratio (HRs) with 95% confidence intervals (CIs)...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28407996/a-multigene-test-could-cost-effectively-help-extend-life-expectancy-for-women-at-risk-of-hereditary-breast-cancer
#14
COMPARATIVE STUDY
Yonghong Li, Andre R Arellano, Lance A Bare, Richard A Bender, Charles M Strom, James J Devlin
BACKGROUND: The National Comprehensive Cancer Network recommends that women who carry gene variants that confer substantial risk for breast cancer consider risk-reduction strategies, that is, enhanced surveillance (breast magnetic resonance imaging and mammography) or prophylactic surgery. Pathogenic variants can be detected in women with a family history of breast or ovarian cancer syndromes by multigene panel testing. OBJECTIVES: To investigate whether using a seven-gene test to identify women who should consider risk-reduction strategies could cost-effectively increase life expectancy...
April 2017: Value in Health: the Journal of the International Society for Pharmacoeconomics and Outcomes Research
https://www.readbyqxmd.com/read/28407687/cytokeratin-19-promoter-directs-the-expression-of-cre-recombinase-in-various-epithelia-of-transgenic-mice
#15
Gui-Feng Zhao, Shuang Zhao, Jia-Jie Liu, Ji-Cheng Wu, Hao-Yu He, Xiao-Qing Ding, Xue-Wen Yu, Ke-Qiang Huang, Zhi-Jie Li, Hua-Chuan Zheng
Cytokeratin 19 (K19) is expressed in various differentiated cells, including gastric, intestinal and bronchial epithelial cells, and liver duct cells. Here, we generated a transgenic mouse line, K19-Cre, in which the expression of Cre recombinase was controlled by the promoter of K19. To test the tissue distribution and excision activity of Cre recombinase, K19-Cre transgenic mice were bred with Rosa26 reporter strain and a mouse strain that carries PTEN conditional alleles (PTENLoxp/Loxp). At mRNA level, Cre was strongly expressed in the stomach, lung and intestine, while in stomach, lung, and liver at protein level...
March 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28403857/hypermethylation-of-cdkn2a-exon-2-in-tumor-tumor-adjacent-and-tumor-distant-tissues-from-breast-cancer-patients
#16
Melanie Spitzwieser, Elisabeth Entfellner, Bettina Werner, Walter Pulverer, Georg Pfeiler, Stefan Hacker, Margit Cichna-Markl
BACKGROUND: Breast carcinogenesis is a multistep process involving genetic and epigenetic changes. Tumor tissues are frequently characterized by gene-specific hypermethylation and global DNA hypomethylation. Aberrant DNA methylation levels have, however, not only been found in tumors, but also in tumor-surrounding tissue appearing histologically normal. This phenomenon is called field cancerization. Knowledge of the existence of a cancer field and its spread are of clinical relevance...
April 12, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28401024/inhibition-of-stat3-signaling-blocks-obesity-induced-mammary-hyperplasia-in-a-mouse-model
#17
Jeong Won Park, Li Zhao, Mark C Willingham, Sheue-Yann Cheng
Compelling epidemiologic evidence indicates that obesity is a risk factor for human cancers, including breast. However, molecular mechanisms by which obesity could contribute to the development of breast cancer remain unclear. To understand the impact of obesity on breast cancer development, we used a mutant mouse that expresses a mutated thyroid hormone receptor β (denoted as PV) with haplodeficiency of the Pten gene (Thrb(PV/PV)Pten(+/-) mice). We previously showed that adult nulliparous female Thrb(PV/PV)Pten(+/-) mice developed extensive mammary hyperplasia and breast tumors...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/28396890/cowden-syndrome-%C3%A2-oral-presentations-of-a-paraneoplastic-syndrome-%C3%A2-case-report-and-review-of-the-literature
#18
Snober Tariq, Joseph Katz
Cowden syndrome is an autosomal dominant disorder with a predisposition to multiple benign and malignant tumors with unique oral manifestations. We present a case of Cowden syndrome in a patient diagnosed with breast cancer, traumatic fibromas, bronchial asthma, and multiple papillomatous fibromatosis of the oral cavity. Close association between oral papillomatosis associated with Cowden syndrome and PTEN gene mutation may increase the risk for malignant transformation. Therefore, patients of Cowden syndrome should be monitored carefully for all kinds of cancers...
2017: Quintessence International
https://www.readbyqxmd.com/read/28386324/mirna-21-promotes-proliferation-and-invasion-of-triple-negative-breast-cancer-cells-through-targeting-pten
#19
Hong Fang, Jiping Xie, Min Zhang, Ziwei Zhao, Yi Wan, Yongqiang Yao
MicroRNAs (miRNAs) are small single-stranded RNAs that bind to the 3'UTR of the mRNAs of target genes. They can target multiple genes and regulate translation or degradation of the mRNA. miRNAs target genes in a tissue-specific manner, and the role of a particular miRNA varies according to tumor origin or even subtype within the same cancer. This study evaluated the effect of miR-21 expression in triple-negative breast cancer (TNBC) tissues and MDA-MB-468, a cell line derived from TNBC tissues. miR-21 was consistently upregulated in TNBC and MDA-MB-468 cells compared to normal tissues...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28358430/comparison-of-the-pi3kca-pathway-in-circulating-tumor-cells-and-corresponding-tumor-tissue-of-patients-with-metastatic-breast-cancer
#20
Maren Bredemeier, Sabine Kasimir-Bauer, Hans-Christian Kolberg, Thomas Herold, Sarah Synoracki, Siegfried Hauch, Philippos Edimiris, Agnes Bankfalvi, Mitra Tewes, Rainer Kimmig, Bahriye Aktas
The aim of the present study was to compare the phosphatidylinositol 3-kinase (PI3KCA)-AKT serine/threonine kinase (AKT) pathway in circulating tumor cells (CTCs) and corresponding cancerous tissues. Stemness‑like circulating tumor cells (slCTCs) and CTCs in epithelial-mesenchymal transition (EMT) have been implicated as the active source of metastatic spread in breast cancer (BC). In this regard, the PI3KCA‑AKT signaling pathway was demonstrated to be implicated in and to be frequently mutated in BC. The present study compared this pathway in slCTCs/CTCs in EMT and the corresponding tumor tissues of 90 metastatic BC patients (pts)...
May 2017: Molecular Medicine Reports
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