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Esophageal cancer pik3ca

Wenqing Yuan, Zhen Liu, Wanjun Lei, Li Sun, Haijun Yang, Yu Wang, Shweta Ramdas, Xiao Dong, Ruiping Xu, Hong Cai, Jun Z Li, Yang Ke
Mixed adenoneuroendocrine carcinoma (MANEC) in the esophagus is an infrequent but highly malignant cancer with few known genomic alterations. We conducted whole-exome sequencing and whole-genome SNP genotyping for 4-6 tumor subregions and 5-6 adjacent normal tissue sites and 1-3 lymph node metastases in two esophageal MANECs to detect somatic mutations and copy number alterations, and to explore their spatial heterogeneity and underlying clonal structure. TP53 mutation, RB1 deletion or LOH, and PIK3CA, PTEN, KRAS, SOX2, DVL3, TP63 amplification appeared in all regions in both tumors...
June 27, 2017: Oncotarget
Russell D Petty, Asa Dahle-Smith, David A J Stevenson, Aileen Osborne, Doreen Massie, Caroline Clark, Graeme I Murray, Susan J Dutton, Corran Roberts, Irene Y Chong, Wasat Mansoor, Joyce Thompson, Mark Harrison, Anirban Chatterjee, Stephen J Falk, Sean Elyan, Angel Garcia-Alonso, David Walter Fyfe, Jonathan Wadsley, Ian Chau, David R Ferry, Zosia Miedzybrodzka
Purpose The Cancer Esophagus Gefitinib trial demonstrated improved progression-free survival with the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor gefitinib relative to placebo in patients with advanced esophageal cancer who had disease progression after chemotherapy. Rapid and durable responses were observed in a minority of patients. We hypothesized that genetic aberration of the EGFR pathway would identify patients benefitting from gefitinib. Methods A prespecified, blinded molecular analysis of Cancer Esophagus Gefitinib trial tumors was conducted to compare efficacy of gefitinib with that of placebo according to EGFR copy number gain (CNG) and EGFR, KRAS, BRAF, and PIK3CA mutation status...
July 10, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Yongxin Ren, Jianming Zheng, Shiming Fan, Linfang Wang, Min Cheng, Dongxia Shi, Wei Zhang, Renxiang Tang, Ying Yu, Longxian Jiao, Jun Ni, Haibin Yang, Huaqing Cai, Fang Yin, Yunxin Chen, Feng Zhou, Weihan Zhang, Weiguo Qing, Weiguo Su
Targeted therapy is not yet approved for esophageal cancer (EC). In this study, we first evaluated EGFR gene and protein expression in 70 Chinese EC patient tumor samples collected during surgery. We then established 23 patient-derived EC xenograft (PDECX) models and assessed the efficacy of theliatinib, a potent and highly selective EGFR inhibitor currently in Phase I clinical study, in 9 PDECX models exhibiting various EGFR expression levels. Immunohistochemical analysis showed that 50 patient tumor samples (71...
April 19, 2017: Oncotarget
Jing-Wei Lin, Xu Li, Ming-Lian Qiu, Rong-Gang Luo, Jian-Bo Lin, Bo Liu
AIMS: The aim of this study was to investigate the association of PI3K expression and PIK3CA mutations with various clinical features in Chinese patients diagnosed with esophageal squamous cell carcinoma (ESCC). METHODS: The study included 112 patients diagnosed with ESCC from Jan 2013 to Dec 2015. Immunohistochemistry was used to determine the expression of PI3K. PIK3CA mutations were determined by sequencing. Statistical analysis was done using SPSS 19.0 software...
April 2017: Genetic Testing and Molecular Biomarkers
Jody C Chuang, Henning Stehr, Ying Liang, Millie Das, Jane Huang, Maximilian Diehn, Heather A Wakelee, Joel W Neal
INTRODUCTION: Erb-b2 receptor tyrosine kinase 2 gene (ERBB2) (also called HER2) has long been recognized as an oncogenic driver in some breast and gastroesophageal cancers in which amplification of this gene confers sensitivity to treatment with Erb-b2 receptor tyrosine kinase 2 (ERBB2)-directed agents. More recently, somatic mutations in ERBB2 have been reported in 1% to 2% of patients with lung adenocarcinoma. Previous case series have suggested clinical tumor responses using anti-ERBB2 small molecules and antibody therapies...
May 2017: Journal of Thoracic Oncology
Jineun Kim, Seoyun Yum, Changwon Kang, Suk-Jo Kang
Cancer arises from complex, multi-layer interactions between diverse genetic and environmental factors. Genetic studies have identified multiple loci associated with tumor susceptibility. However, little is known about how germline polymorphisms interact with one another and with somatic mutations within a tumor to mediate acquisition of cancer traits. Here, we survey recent studies showing gene-gene interactions, also known as epistases, affecting genetic susceptibility in colorectal, gastric and esophageal cancers...
October 11, 2016: Oncotarget
Huili Zheng, Yan Wang, Chuanning Tang, Lindsey Jones, Hua Ye, Guangchun Zhang, Weihai Cao, Jingwen Li, Lifeng Liu, Zhencong Liu, Chao Zhang, Feng Lou, Zhiyuan Liu, Yangyang Li, Zhenfen Shi, Jingbo Zhang, Dandan Zhang, Hong Sun, Haichao Dong, Zhishou Dong, Baishuai Guo, H E Yan, Qingyu Lu, Xue Huang, Si-Yi Chen
BACKGROUND/AIM: Esophageal cancer (EC) is a common malignancy with significant morbidity and mortality. As individual cancers exhibit unique mutation patterns, identifying and characterizing gene mutations in EC that may serve as biomarkers might help predict patient outcome and guide treatment. Traditionally, personalized cancer DNA sequencing was impractical and expensive. Recent technological advancements have made targeted DNA sequencing more cost- and time-effective with reliable results...
May 2016: Cancer Genomics & Proteomics
Hyung Soon Park, Sun Min Lim, Sora Kim, Sangwoo Kim, Hye Ryun Kim, KyuBum Kwack, Min Goo Lee, Joo-Hang Kim, Yong Wha Moon
We evaluated the preliminary efficacy and feasibility of a next-generation sequencing (NGS)-based targeted anticancer therapy in refractory solid tumors at a Korean institution. Thirty-six patients with advanced cancer underwent molecular profiling with NGS with the intent of clinical application of available matched targeted agents. Formalin-fixed paraffin-embedded (FFPE) tumors were sequenced using the Comprehensive Cancer Panel (CCP) or FoundationOne in the Clinical Laboratory Improvement Amendments-certified laboratory in the USA...
2016: PloS One
Shutao Zheng, Chenchen Yang, Mang Lu, Qing Liu, Tao Liu, Fang Dai, Xiangpeng Gao, Ilyar Sheyhidin, Xiaomei Lu
The PIK3CA mutation has been extensively reported in the setting of cancers; however, the clinicopathological significance of PIK3CA expression has rarely been discussed in esophageal squamous cell carcinoma. In the present study, to confirm the significance of PIK3CA expression in association with metastasis and prognosis, which has been somewhat controversial in esophageal squamous cell carcinoma (ESCC), the relationship between clinicopathological features of ESCC and PIK3CA expression was analyzed using immunohistochemistry with a tissue microarray...
July 2016: Human Pathology
Yasushi Sasaki, Miyuki Tamura, Ryota Koyama, Takafumi Nakagaki, Yasushi Adachi, Takashi Tokino
Two major types of cancer occur in the esophagus: squamous cell carcinoma, which is associated with chronic smoking and alcohol consumption, and adenocarcinoma, which typically arises in gastric reflux-associated Barrett's esophagus. Although there is increasing incidence of esophageal adenocarcinoma in Western counties, esophageal squamous cell carcinoma (ESCC) accounts for most esophageal malignancies in East Asia, including China and Japan. Technological advances allowing for massively parallel, high-throughput next-generation sequencing (NGS) of DNA have enabled comprehensive characterization of somatic mutations in large numbers of tumor samples...
February 21, 2016: World Journal of Gastroenterology: WJG
Keisuke Kosumi, Yoshifumi Baba, Takatsugu Ishimoto, Kazuto Harada, Kenichi Nakamura, Mayuko Ohuchi, Yuki Kiyozumi, Daisuke Izumi, Ryuma Tokunaga, Katsunobu Taki, Takaaki Higashi, Tatsunori Miyata, Hironobu Shigaki, Junji Kurashige, Yukiharu Hiyoshi, Masaaki Iwatsuki, Shiro Iwagami, Yasuo Sakamoto, Yuji Miyamoto, Naoya Yoshida, Eiji Oki, Masayuki Watanabe, Hideo Baba
APOBEC3B belongs to the cytidine deaminase apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like (APOBEC3) family of enzymes and induces C to T transitions of target DNA by cytidine deamination. Recently, several mutations in various cancers have been linked to APOBEC3B, suggesting a crucial role for this protein in carcinogenesis and cancer development. However, the significance of APOBEC3B in esophageal squamous cell carcinoma (ESCC) remains uncertain. In addition, the APOBEC3B immunoreactivity in cancer tissues is uncertain...
March 2016: Medical Oncology
Genta Sawada, Atsushi Niida, Ryutaro Uchi, Hidenari Hirata, Teppei Shimamura, Yutaka Suzuki, Yuichi Shiraishi, Kenichi Chiba, Seiya Imoto, Yusuke Takahashi, Takeshi Iwaya, Tomoya Sudo, Tomoatsu Hayashi, Hiroki Takai, Yoshihiro Kawasaki, Takashi Matsukawa, Hidetoshi Eguchi, Keishi Sugimachi, Fumiaki Tanaka, Hiromichi Suzuki, Ken Yamamoto, Hideshi Ishii, Makiko Shimizu, Hiroshi Yamazaki, Makoto Yamazaki, Yuji Tachimori, Yoshiaki Kajiyama, Shoji Natsugoe, Hiromasa Fujita, Kenichi Mafune, Yoichi Tanaka, David P Kelsell, Claire A Scott, Shoji Tsuji, Shinichi Yachida, Tatsuhiro Shibata, Sumio Sugano, Yuichiro Doki, Tetsu Akiyama, Hiroyuki Aburatani, Seishi Ogawa, Satoru Miyano, Masaki Mori, Koshi Mimori
BACKGROUND & AIMS: Esophageal squamous cell carcinoma (ESCC) is the predominant form of esophageal cancer in Japan. Smoking and drinking alcohol are environmental risk factors for ESCC, whereas single nucleotide polymorphisms in ADH1B and ALDH2, which increase harmful intermediates produced by drinking alcohol, are genetic risk factors. We conducted a large-scale genomic analysis of ESCCs from patients in Japan to determine the mutational landscape of this cancer. METHODS: We performed whole-exome sequence analysis of tumor and nontumor esophageal tissues collected from 144 patients with ESCC who underwent surgery at 5 hospitals in Japan...
May 2016: Gastroenterology
Yuanyuan Wu, Xi Liu, Liwen Hu, Huansheng Tao, Xingying Guan, Kun Zhang, Yun Bai, Kang Yang
PURPOSE: Esophageal squamous cell carcinoma (ESCC) is one of the most fatal cancers worldwide. However, the etiology is complex and unclear. 3q26 harboring abundant oncogenes have been identified as the loci of ESCC susceptibility. In the present study, we examined whether CNVs on 3q26 would be associated with the risk, TNM stage and prognosis of ESCC. METHODS: Variation_91720 in phosphatidylinositol 3-kinase catalytic subunit (PIK3CA) and Variation_91733 in sex-determining region Y-box 2 overlapping transcript (SOX2OT) were selected for investigation...
2015: International Journal of Clinical and Experimental Pathology
Caixia Cheng, Heyang Cui, Ling Zhang, Zhiwu Jia, Bin Song, Fang Wang, Yaoping Li, Jing Liu, Pengzhou Kong, Ruyi Shi, Yanghui Bi, Bin Yang, Juan Wang, Zhenxiang Zhao, Yanyan Zhang, Xiaoling Hu, Jie Yang, Chanting He, Zhiping Zhao, Jinfen Wang, Yanfeng Xi, Enwei Xu, Guodong Li, Shiping Guo, Yunqing Chen, Xiaofeng Yang, Xing Chen, Jianfang Liang, Jiansheng Guo, Xiaolong Cheng, Chuangui Wang, Qimin Zhan, Yongping Cui
BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is the sixth most lethal cancer worldwide and the fourth most lethal cancer in China. Genomic characterization of tumors, particularly those of different stages, is likely to reveal additional oncogenic mechanisms. Although copy number alterations and somatic point mutations associated with the development of ESCC have been identified by array-based technologies and genome-wide studies, the genomic characterization of ESCCs from different stages of the disease has not been explored...
2016: GigaScience
Kai Wang, Adrienne Johnson, Siraj M Ali, Samuel J Klempner, Tanios Bekaii-Saab, Jeffrey L Vacirca, Depinder Khaira, Roman Yelensky, Juliann Chmielecki, Julia A Elvin, Doron Lipson, Vincent A Miller, Philip J Stephens, Jeffrey S Ross
BACKGROUND: Esophageal squamous cell carcinomas (ESCCs) and esophageal adenocarcinomas (EACs) account for >95% of esophageal malignancies and represent a major global health burden. ESCC is the dominant histology globally but represents a minority of U.S. cases, with EAC accounting for the majority of U.S. CASES: The patient outcomes for advanced ESCC and EAC are poor, and new therapeutic options are needed. Using a sensitive sequencing assay, we compared the genomic profiles of ESCC and EAC with attention to identification of therapeutically relevant genomic alterations...
October 2015: Oncologist
Yelena Y Janjigian, Efsevia Vakiani, Geoffrey Y Ku, Jessica M Herrera, Laura H Tang, Nancy Bouvier, Agnès Viale, Nicholas D Socci, Marinela Capanu, Michael Berger, David H Ilson
PURPOSE: Vascular endothelial growth factor receptor (VEGFR2) directed therapies result in a modest survival benefit for patients with advanced esophageal and gastroesophageal (GE) junction cancer. Platelet-derived growth factor receptor (PDGFR) may contribute to escape from VEGFR2 inhibition. We evaluated the efficacy of sorafenib, a broad spectrum tyrosine kinase inhibitor targeting VEGFR2 and PDGFR as well as RET and RAF1, in patients with metastatic chemotherapy refractory esophageal and GE junction cancer...
2015: PloS One
Konstantia E Tasioudi, Stratigoula Sakellariou, Georgia Levidou, Dimitrios Theodorou, Nikolaos V Michalopoulos, Efstratios Patsouris, Penelope Korkolopoulou, Angelica A Saetta
Among the numerous signaling pathways involved in tumorigenesis, PI3K-AKT-mTOR is a key one that regulates diverse cellular functions. However, its prognostic value in esophageal carcinoma remains unclear. In our study, we examined the immunohistochemical expression of phosphorylated (p-) AKT, mTOR, p70S6K and 4E-BP1 along with the mutational status of PIK3CA and AKT1 genes by High Resolution Melting Analysis and Pyrosequencing in 44 esophageal carcinomas. The results were correlated with the clinicopathological characteristics of the patients in an effort to define their possible prognostic significance...
August 2015: APMIS: Acta Pathologica, Microbiologica, et Immunologica Scandinavica
Ling Zhang, Yong Zhou, Caixia Cheng, Heyang Cui, Le Cheng, Pengzhou Kong, Jiaqian Wang, Yin Li, Wenliang Chen, Bin Song, Fang Wang, Zhiwu Jia, Lin Li, Yaoping Li, Bin Yang, Jing Liu, Ruyi Shi, Yanghui Bi, Yanyan Zhang, Juan Wang, Zhenxiang Zhao, Xiaoling Hu, Jie Yang, Hongyi Li, Zhibo Gao, Gang Chen, Xuanlin Huang, Xukui Yang, Shengqing Wan, Chao Chen, Bin Li, Yongkai Tan, Longyun Chen, Minghui He, Sha Xie, Xiangchun Li, Xuehan Zhuang, Mengyao Wang, Zhi Xia, Longhai Luo, Jie Ma, Bing Dong, Jiuzhou Zhao, Yongmei Song, Yunwei Ou, Enming Li, Liyan Xu, Jinfen Wang, Yanfeng Xi, Guodong Li, Enwei Xu, Jianfang Liang, Xiaofeng Yang, Jiansheng Guo, Xing Chen, Yanbo Zhang, Qingshan Li, Lixin Liu, Yingrui Li, Xiuqing Zhang, Huanming Yang, Dongxin Lin, Xiaolong Cheng, Yongjun Guo, Jun Wang, Qimin Zhan, Yongping Cui
Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers worldwide and the fourth most lethal cancer in China. However, although genomic studies have identified some mutations associated with ESCC, we know little of the mutational processes responsible. To identify genome-wide mutational signatures, we performed either whole-genome sequencing (WGS) or whole-exome sequencing (WES) on 104 ESCC individuals and combined our data with those of 88 previously reported samples. An APOBEC-mediated mutational signature in 47% of 192 tumors suggests that APOBEC-catalyzed deamination provides a source of DNA damage in ESCC...
April 2, 2015: American Journal of Human Genetics
John T Miura, Joanne Xiu, James Thomas, Ben George, Benjamin R Carron, Susan Tsai, Fabian M Johnston, Kiran K Turaga, T Clark Gamblin
BACKGROUND: NCCN states that chemotherapies for advanced esophageal and gastric cancers may be used interchangeably. Biomarkers from gastroesophageal cancer patients were interrogated to identify actionable alterations with therapeutic implications. METHODS: 666 gastric and 640 esophageal cancer cases referred to Caris Life Sciences between 2009 thru 2013 were evaluated. Specific testing was performed, which included a combination of sequencing (Sanger, NGS) and protein expression (IHC)...
2015: Cancer Biology & Therapy
Yoshifumi Baba, Takatsugu Ishimoto, Kazuto Harada, Keisuke Kosumi, Asuka Murata, Keisuke Miyake, Yukiharu Hiyoshi, Junji Kurashige, Masaaki Iwatsuki, Shiro Iwagami, Yuji Miyamoto, Yasuo Sakamoto, Naoya Yoshida, Eiji Oki, Ken-Ichi Iyama, Masayuki Watanabe, Hideo Baba
BACKGROUND: Basaloid squamous cell carcinoma (BSCC) of the esophagus is a rare carcinoma with distinct characteristics, and was recently recognized as a variant of squamous cell carcinoma (SCC). We previously revealed genetic and epigenetic alterations associated with esophageal SCCs in relation to clinical outcome, including mutations in KRAS, BRAF, and PIK3CA, p53 expression, and long interspersed nucleotide element-1 (LINE-1) methylation, a surrogate marker for global DNA methylation level...
October 2015: Annals of Surgical Oncology
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