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https://www.readbyqxmd.com/read/28636652/integrative-analysis-of-genomic-alterations-in-triple-negative-breast-cancer-in-association-with-homologous-recombination-deficiency
#1
Masahito Kawazu, Shinya Kojima, Toshihide Ueno, Yasushi Totoki, Hiromi Nakamura, Akiko Kunita, Wei Qu, Jun Yoshimura, Manabu Soda, Takahiko Yasuda, Natsuko Hama, Mihoko Saito-Adachi, Kazuhito Sato, Shinji Kohsaka, Eirin Sai, Masako Ikemura, Shigeru Yamamoto, Tomoko Ogawa, Masashi Fukayama, Keiichiro Tada, Yasuyuki Seto, Shinichi Morishita, Shoichi Hazama, Tatsuhiro Shibata, Yoshihiro Yamashita, Hiroyuki Mano
Triple-negative breast cancer (TNBC) cells do not express estrogen receptors, progesterone receptors, or human epidermal growth factor receptor 2. Currently, apart from poly ADP-ribose polymerase inhibitors, there are few effective therapeutic options for this type of cancer. Here, we present comprehensive characterization of the genetic alterations in TNBC performed by high coverage whole genome sequencing together with transcriptome and whole exome sequencing. Silencing of the BRCA1 gene impaired the homologous recombination pathway in a subset of TNBCs, which exhibited similar phenotypes to tumors with BRCA1 mutations; they harbored many structural variations (SVs) with relative enrichment for tandem duplication...
June 21, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28620008/pten-dicer1-fh-and-their-associated-tumor-susceptibility-syndromes-clinical-features-genetics-and-surveillance-recommendations-in-childhood
#2
REVIEW
Kris Ann P Schultz, Surya P Rednam, Junne Kamihara, Leslie Doros, Maria Isabel Achatz, Jonathan D Wasserman, Lisa R Diller, Laurence Brugières, Harriet Druker, Katherine A Schneider, Rose B McGee, William D Foulkes
PTEN hamartoma tumor syndrome (PHTS), DICER1 syndrome, and hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome are pleiotropic tumor predisposition syndromes that include benign and malignant neoplasms affecting adults and children. PHTS includes several disorders with shared and distinct clinical features. These are associated with elevated lifetime risk of breast, thyroid, endometrial, colorectal, and renal cancers as well as melanoma. Thyroid cancer represents the predominant cancer risk under age 20 years...
June 15, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28608266/potentially-pathogenic-germline-chek2-c-319-2t-a-among-multiple-early-onset-cancer-families
#3
Mev Dominguez-Valentin, Sigve Nakken, Hélène Tubeuf, Daniel Vodak, Per Olaf Ekstrøm, Anke M Nissen, Monika Morak, Elke Holinski-Feder, Alexandra Martins, Pål Møller, Eivind Hovig
To study the potential contribution of genes other than BRCA1/2, PTEN, and TP53 to the biological and clinical characteristics of multiple early-onset cancers in Norwegian families, including early-onset breast cancer, Cowden-like and Li-Fraumeni-like syndromes (BC, CSL and LFL, respectively). The Hereditary Cancer Biobank from the Norwegian Radium Hospital was used to identify early-onset BC, CSL or LFL for whom no pathogenic variants in BRCA1/2, PTEN, or TP53 had been found in routine diagnostic DNA sequencing...
June 12, 2017: Familial Cancer
https://www.readbyqxmd.com/read/28607685/concurrent-braf-and-pten-mutations-in-melanoma-of-unknown-origin-presenting-as-a-breast-mass
#4
Emmanuel Agosto-Arroyo, Marilin Rosa, Alec Chau, Laila Khazai
BACKGROUND: Metastases represent a small percentage of the malignancies affecting the breast, and only 5% of melanomas originate from non-cutaneous sites. Multiple genetic aberrations have been associated with the development of melanocytic lesions, including BRAF V600E mutation. Mutations in PTEN gene have also been related to the pathogenesis of multiple malignancies. PURPOSE/METHOD: This is the case of a 28-year-old female who presented with a tender, palpable mass in the upper outer quadrant of the right breast...
2017: SAGE open medical case reports
https://www.readbyqxmd.com/read/28606050/insights-into-the-targeting-potential-of-thymoquinone-for-therapeutic-intervention-against-triple-negative-breast-cancer
#5
Md Abul Barkat, Harshita Abul, Javed Ahmad, Mohammad Ahmed Khan, Sarwar Beg, Farhan Jalees Ahmad
BACKGROUND: Thymoquinone (TQ) is a bioactive phytoconstituent obtained from Nigella sativa (black seeds). It has promising potential in cancer prevention. OBJECTIVE: Previous studies have shown that TQ can modulate signaling pathways responsible for cancer progression, thus enhances the efficacy and improve safety profile of clinically used anticancer drugs. METHOD: TQ acts on cell cycle and inhibits progression from G1 to S phase by targeting various proteins (cyclin D1, cyclin E, and p27)...
June 11, 2017: Current Drug Targets
https://www.readbyqxmd.com/read/28599484/anticancer-effect-of-curcumin-inhibits-cell-growth-through-mir-21-pten-akt-pathway-in-breast-cancer-cell
#6
Xinzheng Wang, Yakai Hang, Jinbiao Liu, Yongqiang Hou, Ning Wang, Mingjun Wang
Curcumin is a polyphenol extracted from turmeric, which that belongs to the Zingiberaceae family. Curcumin has numerous effects, including anti-inflammatory, antitumor, anti-oxidative and antimicrobial effects. However, the effects of curcumin on human breast cancer cells remain largely unknown. The aim of the present study was to investigate the anticancer effects and the mechanisms by which curcumin affects breast cancer cells. The anticancer effect of curcumin on cell viability and cytotoxicity on human breast cancer MCF-7 cells was analyzed using 3-(4,5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H-tetrazolium bromide and lactate dehydrogenase assays, respectively...
June 2017: Oncology Letters
https://www.readbyqxmd.com/read/28594745/indications-for-contralateral-prophylactic-mastectomy-a-consensus-statement-using-modified-delphi-methodology
#7
Frances C Wright, Nicole J Look Hong, May Lynn Quan, Kaitlyn Beyfuss, Sara Temple, Andrea Covelli, Nancy Baxter, Anna R Gagliardi
OBJECTIVE: To reach a consensus about contralateral prophylactic mastectomy in unilateral breast cancer. SUMMARY BACKGROUND DATA: There has been a substantial increase in the number of North American women with unilateral breast cancer undergoing a therapeutic mastectomy and a contralateral prophylactic mastectomy (CPM) either simultaneously or sequentially. The purpose of this project was to create a nationally endorsed consensus statement for CPM in women with unilateral breast cancer using modified Delphi consensus methodology...
June 7, 2017: Annals of Surgery
https://www.readbyqxmd.com/read/28559303/trpc1-is-a-differential-regulator-of-hypoxia-mediated-events-and-akt-signaling-in-pten-deficient-breast-cancer-cells
#8
Iman Azimi, Michael J G Milevskiy, Elke Kaemmerer, Dane Turner, Kunsala T D S Yapa, Melissa A Brown, Erik W Thompson, Sarah J Roberts-Thomson, Gregory R Monteith
Hypoxia is a feature of the tumour microenvironment and promotes invasiveness, resistance to chemotherapeutics and cell survival. Our studies identify the transient receptor potential canonical-1 (TRPC1) ion channel as a key component of responses to hypoxia in breast cancer cells. This regulation includes control of specific epithelial to mesenchymal transition (EMT) events and hypoxia-mediated activation of signaling pathways such as activation of the EGFR, STAT3 and the autophagy marker LC3B, through hypoxia-inducible factor-1alpha (HIF1α)-dependent and -independent mechanisms...
May 30, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28539722/effect-of-helix-aspersa-extract-on-tnf%C3%AE-nf-%C3%AE%C2%BAb-and-some-tumor-suppressor-genes-in-breast-cancer-cell-line-hs578t
#9
Ibtissem El Ouar, Cornelia Braicu, Dalila Naimi, Alexendru Irimie, Ioana Berindan-Neagoe
BACKGROUND: The garden snail, Helix aspersa, is a big land snail widely found in the Mediterranean countries. It is one of the most consumed species and widely used in zootherapy. OBJECTIVE: The present study was carried out to investigate for the first time the first time the antitumor activity of an aqueous extract from Helix aspersa. MATERIALS AND METHODS: The effect of H. aspersa extract was studied on a triple negative breast cancer cell line Hs578T...
April 2017: Pharmacognosy Magazine
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
#10
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
#11
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
#12
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
#13
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
#14
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 STAT3 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)...
August 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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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