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https://www.readbyqxmd.com/read/28088513/an-immunogram-for-the-cancer-immunity-cycle-towards-personalized-immunotherapy-of-lung-cancer
#1
Takahiro Karasaki, Kazuhiro Nagayama, Hideki Kuwano, Jun-Ichi Nitadori, Masaaki Sato, Masaki Anraku, Akihiro Hosoi, Hirokazu Matsushita, Yasuyuki Morishita, Kosuke Kashiwabara, Masaki Takazawa, Osamu Ohara, Kazuhiro Kakimi, Jun Nakajima
INTRODUCTION: The interaction of immune cells and cancer cells shapes the immunosuppressive tumor microenvironment. For successful cancer immunotherapy, comprehensive knowledge of anti-tumor immunity as a dynamic spacio-temporal process is required for each individual patient. To this end, we developed an immunogram for the cancer-immunity cycle using next-generation sequencing. METHODS: Whole-exome sequencing and RNA-Seq was performed in 20 non-small cell lung cancer patients (12 adenocarcinoma, 7 squamous cell carcinoma, and 1 large cell neuroendocrine carcinoma)...
January 11, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28088511/brief-report-egfr-l858m-l861q-cis-mutations-confer-selective-sensitivity-to-afatinib
#2
Jamie A Saxon, Lynette M Sholl, Pasi A Jänne
INTRODUCTION: Tyrosine kinase inhibitors (TKIs) have been developed to treat patients with epidermal growth factor receptor (EGFR)-mutant lung cancers. However, the therapeutic efficacy of TKIs in patients with uncommon EGFR mutations remains unclear. METHODS: Next-generation sequencing was performed on a patient's lung adenocarcinoma tumor sample, revealing rare combined in cis (on the same allele) EGFR mutations. Stable Ba/F3 and NIH-3T3 cell lines harboring the mutations were established to investigate the effect of first, second, and third generation EGFR TKIs on cell proliferation by MTS assay and EGFR phosphorylation by Western blotting...
January 11, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28088228/the-loss-of-function-mutations-and-down-regulated-expression-of-asb3-gene-promote-the-growth-and-metastasis-of-colorectal-cancer-cells
#3
Wu-Ying Du, Zhen-Hai Lu, Wen Ye, Xiang Fu, Yi Zhou, Chun-Mei Kuang, Jiang-Xue Wu, Zhi-Zhong Pan, Shuai Chen, Ran-Yi Liu, Wen-Lin Huang
BACKGROUND: Ankyrin repeat and SOCS box protein 3 (ASB3) is a member of ASB family and contains ankyrin repeat sequence and SOCS box domain. Previous studies indicated that it mediates the ubiquitination and degradation of tumor necrosis factor receptor 2 and is likely involved in inflammatory responses. However, its effects on oncogenesis are unclear. This study aimed to investigate the effects of ASB3 on the growth and metastasis of colorectal cancer (CRC). METHODS: We used next-generation sequencing or Sanger sequencing to detect ASB3 mutations in CRC specimens or cell lines, and used real-time quantitative polymerase chain reaction, Western blotting, and immunohistochemical or immunofluorescence assay to determine gene expression...
January 14, 2017: Chinese Journal of Cancer
https://www.readbyqxmd.com/read/28081303/the-novel-fusion-transcript-nr5a2-klhl29ft-is-generated-by-an-insertion-at-the-klhl29-locus
#4
Zhenguo Sun, Xiquan Ke, Steven L Salzberg, Daehwan Kim, Valentin Antonescu, Yulan Cheng, Binbin Huang, Jee Hoon Song, John M Abraham, Sariat Ibrahim, Hui Tian, Stephen J Meltzer
BACKGROUND: Novel fusion transcripts (FTs) caused by chromosomal rearrangement are common factors in the development of cancers. In the current study, the authors used massively parallel RNA sequencing to identify new FTs in colon cancers. METHODS: RNA sequencing (RNA-Seq) and TopHat-Fusion were used to identify new FTs in colon cancers. The authors then investigated whether the novel FT nuclear receptor subfamily 5, group A, member 2 (NR5A2)-Kelch-like family member 29 FT (KLHL29FT) was transcribed from a genomic chromosomal rearrangement...
January 12, 2017: Cancer
https://www.readbyqxmd.com/read/28079881/translational-upregulation-of-aurora-a-by-hnrnp-q1-contributes-to-cell-proliferation-and-tumorigenesis-in-colorectal-cancer
#5
Chien-Hsien Lai, Yu-Chuan Huang, Jenq-Chang Lee, Joseph Ta-Chien Tseng, Kung-Chao Chang, Yen-Ju Chen, Nai-Jhu Ding, Pao-Hsuan Huang, Wen-Chang Chang, Bo-Wen Lin, Ruo-Yu Chen, Yu-Chu Wang, Yi-Chien Lai, Liang-Yi Hung
By using RNA-immunoprecipitation assay following next-generation sequencing, a group of cell cycle-related genes targeted by hnRNP Q1 were identified, including Aurora-A kinase. Overexpressed hnRNP Q1 can upregulate Aurora-A protein, but not alter the mRNA level, through enhancing the translational efficiency of Aurora-A mRNA, either in a cap-dependent or -independent manner, by interacting with the 5'-UTR of Aurora-A mRNA through its RNA-binding domains (RBDs) 2 and 3. By ribosomal profiling assay further confirmed the translational regulation of Aurora-A mRNA by hnRNP Q1...
January 12, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28079877/genome-wide-transposon-screening-and-quantitative-insertion-site-sequencing-for-cancer-gene-discovery-in-mice
#6
Mathias J Friedrich, Lena Rad, Iraad F Bronner, Alexander Strong, Wei Wang, Julia Weber, Matthew Mayho, Hannes Ponstingl, Thomas Engleitner, Carolyn Grove, Anja Pfaus, Dieter Saur, Juan Cadiñanos, Michael A Quail, George S Vassiliou, Pentao Liu, Allan Bradley, Roland Rad
Transposon-mediated forward genetics screening in mice has emerged as a powerful tool for cancer gene discovery. It pinpoints cancer drivers that are difficult to find with other approaches, thus complementing the sequencing-based census of human cancer genes. We describe here a large series of mouse lines for insertional mutagenesis that are compatible with two transposon systems, PiggyBac and Sleeping Beauty, and give guidance on the use of different engineered transposon variants for constitutive or tissue-specific cancer gene discovery screening...
February 2017: Nature Protocols
https://www.readbyqxmd.com/read/28078645/parp-inhibitors-in-reproductive-system-cancers-current-use-and-developments
#7
REVIEW
Geraldine O'Sullivan Coyne, Alice P Chen, Robert Meehan, James H Doroshow
The repair of DNA damage is a critical cellular process governed by multiple biochemical pathways that are often found to be defective in cancer cells. The poly(ADP-ribose) polymerase (PARP) family of proteins controls response to single-strand DNA breaks by detecting these damaged sites and recruiting the proper factors for repair. Blocking this pathway forces cells to utilize complementary mechanisms to repair DNA damage. While PARP inhibition may not, in itself, be sufficient to cause tumor cell death, inhibition of DNA repair with PARP inhibitors is an effective cytotoxic strategy when it is used in patients who carry other defective DNA-repair mechanisms, such as mutations in the genes BRCA 1 and 2...
January 11, 2017: Drugs
https://www.readbyqxmd.com/read/28078112/molecular-spectrum-of-kras-nras-braf-pik3ca-tp53-and-apc-somatic-gene-mutations-in-arab-patients-with-colorectal-cancer-determination-of-frequency-and-distribution-pattern
#8
Humaid O Al-Shamsi, Jeremy Jones, Yazan Fahmawi, Ibrahim Dahbour, Aziz Tabash, Reham Abdel-Wahab, Ahmed O S Abousamra, Kenna R Shaw, Lianchun Xiao, Manal M Hassan, Benjamin R Kipp, Scott Kopetz, Amr S Soliman, Robert R McWilliams, Robert A Wolff
BACKGROUND: The frequency rates of mutations such as KRAS, NRAS, BRAF, and PIK3CA in colorectal cancer (CRC) differ among populations. The aim of this study was to assess mutation frequencies in the Arab population and determine their correlations with certain clinicopathological features. METHODS: Arab patients from the Arab Gulf region and a population of age- and sex-matched Western patients with CRC whose tumors were evaluated with next-generation sequencing (NGS) were identified and retrospectively reviewed...
December 2016: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28076841/clonal-evolution-in-therapy-related-neoplasms
#9
Emiliano Fabiani, Giulia Falconi, Luana Fianchi, Marianna Criscuolo, Tiziana Ottone, Laura Cicconi, Stefan Hohaus, Simona Sica, Massimiliano Postorino, Antonino Neri, Marta Lionetti, Giuseppe Leone, Francesco Lo-Coco, Maria Teresa Voso
Therapy-related myeloid neoplasms (t-MN) may occur as a late effect of cytotoxic therapy for a primary malignancy or autoimmune diseases in susceptible individuals. We studied the development of somatic mutations in t-MN, using a collection of follow-up samples from 14 patients with a primary hematologic malignancy, who developed a secondary leukemia (13 t-MN and 1 t-acute lymphoblastic leukemia), at a median latency of 73 months (range 18-108) from primary cancer diagnosis.Using Sanger and next generation sequencing (NGS) approaches we identified 8 mutations (IDH1 R132H, ASXL1 Y591*, ASXL1 S689*, ASXL1 R693*, SRSF2 P95H, SF3B1 K700E, SETBP1 G870R and TP53 Y220C) in seven of thirteen t-MN patients (54%), whereas the t-ALL patient had a t(4,11) translocation, resulting in the KMT2A/AFF1 fusion gene...
January 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28075483/detecting-apc-gene-mutations-in-familial-adenomatous-polyposis-fap
#10
Babi Ramesh Reddy Nallamilli, Madhuri Hegde
Hereditary forms of colorectal cancer (CRC) account for up to 5% of total cases. Familial adenomatous polyposis (FAP) is an autosomal dominant condition affecting nearly 1 in 5000 people and accounts for only about 1% of all CRCs. It is characterized by the progressive development of hundreds to thousands of adenomatous colon polyps. The gene associated with FAP (APC) contains 15 coding exons. The mutation spectrum of the APC gene is broad in that 87% of causative mutations are point mutations (including other sequence variants) and around 10% to 15% are intragenic deletions and duplications...
January 11, 2017: Current Protocols in Human Genetics
https://www.readbyqxmd.com/read/28073683/mutant-allele-tumor-heterogeneity-scores-correlate-with-risk-of-metastases-in-colon%C3%A2-cancer
#11
Ashwani Rajput, Thèrése Bocklage, Alissa Greenbaum, Ji-Hyun Lee, Scott A Ness
BACKGROUND: Colorectal cancer is a leading cause of cancer-related mortality, has a very broad mutational spectrum, and there is no clinically available biomarker that can predict which patients with stage II or stage III colorectal cancer will develop metastatic disease. PATIENTS AND METHODS: We used a targeted next-generation sequencing approach to analyze the mutational spectra in stage II and III colon cancer patient samples. RESULTS: Amidst a broad range of acquired mutations and variants, we found evidence of tumor heterogeneity that distinguished the tumors in different groups...
November 23, 2016: Clinical Colorectal Cancer
https://www.readbyqxmd.com/read/28069683/targeted-deep-sequencing-reveals-full-methylation-profiles-of-multiple-hpv-types-and-potential-biomarkers-for-cervical-cancer-progression
#12
Pengyuan Liu, Marissa Iden, Samantha Fye, Yi-Wen Huang, Elizabeth Hopp, Chen Chu, Yan Lu, Janet S Rader
BACKGROUND: Invasive cervical cancer (ICC) and its premalignant phase (cervical intraepithelial neoplasia; CIN1-3) are distinguished by gynecological and pathological examination, yet no current methodologies can predict precancerous lesions that are destined to progress to ICC. Thus, development of reliable assays to assess patient prognosis is much needed. METHODS: HPV DNA methylation is significantly altered in cervical disease. Using an HPV-enrichment approach and next-generation DNA sequencing, methylation status was characterized in a case-case comparison of CIN (n = 2 CIN1; n = 2 CIN2; n = 20 CIN3) and ICC (n = 37) samples...
January 9, 2017: Cancer Epidemiology, Biomarkers & Prevention
https://www.readbyqxmd.com/read/28068482/metabolic-reprogramming-in-brain-tumors
#13
Sriram Venneti, Craig B Thompson
Next-generation sequencing has substantially enhanced our understanding of the genetics of primary brain tumors by uncovering several novel driver genetic alterations. How many of these genetic modifications contribute to the pathogenesis of brain tumors is not well understood. An exciting paradigm emerging in cancer biology is that oncogenes actively reprogram cellular metabolism to enable tumors to survive and proliferate. We discuss how some of these genetic alterations in brain tumors rewire metabolism...
December 21, 2016: Annual Review of Pathology
https://www.readbyqxmd.com/read/28067073/translating-genomic-profiling-to-gastrointestinal-cancer-treatment
#14
Kazuto Harada, Dilsa Mizrak Kaya, Yusuke Shimodaira, Shumei Song, Hideo Baba, Jaffer A Ajani
Next-generation sequencing enables faster, cheaper and more accurate whole-genome sequencing, allowing genome profiling and discovery of molecular features. As molecular targeted drugs are developed, treatment can be tailored according to molecular subtype. Gastric and colorectal cancers have each been divided into four subtypes according to molecular features. Profiling of the esophageal cancer genome is underway and its classification is anticipated. To date, identification of HER2 expression in gastric adenocarcinoma and KRAS, NRAS and BRAF mutations in colon cancer have proved essential for treatment decisions...
January 9, 2017: Future Oncology
https://www.readbyqxmd.com/read/28065930/rapid-changes-in-circulating-tumor-dna-in-serially-sampled-plasma-during-treatment-of-breast-cancer-a-case-report
#15
Hiroshi Nakagomi, Yosuke Hirotsu, Kenji Amemiya, Haruka Nakada, Masayuki Inoue, Hitoshi Mochizuki, Toshio Oyama, Masao Omata
BACKGROUND The analysis of circulating tumor DNA (ctDNA) is expected to be a modality to determine the status of cancer in real time. This case indicated utilities and issues in measuring the ctDNA in cancer patients. CASE REPORT A 45-year-old woman with metastatic breast cancer was treated with bevacizumab and paclitaxel. The lung metastases were decreased but the meningitis carcinoma developed rapidly and she died. During the treatment with bevacizumab and paclitaxel, blood samples were taken serially and ctDNA was analyzed using a next-generation sequencer...
January 9, 2017: American Journal of Case Reports
https://www.readbyqxmd.com/read/28061482/genomic-mutation-driven-metastatic-breast-cancer-therapy-a-single-center-experience
#16
Yuan Yuan, Susan E Yost, Yate-Ching Yuan, Nicola M Solomon, Isa Mambetsariev, Sumanta Pal, Paul Frankel, Ravi Salgia, Susan L Neuhausen, Joanne Mortimer
BACKGROUND: Next-Generation Sequencing (NGS) has made genomic mutation-driven therapy feasible for metastatic breast cancer (MBC) patients. We frequently submit tumor tissue from MBC patients for targeted NGS of tumor using the Illumina HiSeq 2000 platform (FoundationOne®, Foundation Medicine, MA). Herein, we report the results and clinical impact of this test in MBC patients. PATIENTS AND METHODS: We identified patients with MBC treated at City of Hope from January 2014 to May 2016 who underwent NGS...
January 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28060956/technical-insights-into-highly-sensitive-isolation-and-molecular-characterization-of-fixed-and-live-circulating-tumor-cells-for-early-detection-of-tumor-invasion
#17
Sophie Laget, Lucile Broncy, Katia Hormigos, Dalia M Dhingra, Fatima BenMohamed, Thierry Capiod, Magne Osteras, Laurent Farinelli, Stephen Jackson, Patrizia Paterlini-Bréchot
Circulating Tumor Cells (CTC) and Circulating Tumor Microemboli (CTM) are Circulating Rare Cells (CRC) which herald tumor invasion and are expected to provide an opportunity to improve the management of cancer patients. An unsolved technical issue in the CTC field is how to obtain highly sensitive and unbiased collection of these fragile and heterogeneous cells, in both live and fixed form, for their molecular study when they are extremely rare, particularly at the beginning of the invasion process. We report on a new protocol to enrich from blood live CTC using ISET® (Isolation by SizE of Tumor/Trophoblastic Cells), an open system originally developed for marker-independent isolation of fixed tumor cells...
2017: PloS One
https://www.readbyqxmd.com/read/28058815/small-rnaome-profiling-from-human-skeletal-muscle-novel-mirnas-and-their-targets-associated-with-cancer-cachexia
#18
Ashok Narasimhan, Sunita Ghosh, Cynthia Stretch, Russell Greiner, Oliver F Bathe, Vickie Baracos, Sambasivarao Damaraju
BACKGROUND: MicroRNAs (miRs) are small non-coding RNAs that regulate gene (mRNA) expression. Although the pathological role of miRs have been studied in muscle wasting conditions such as myotonic and muscular dystrophy, their roles in cancer cachexia (CC) are still emerging. OBJECTIVES: The objectives are (i) to profile human skeletal muscle expressed miRs; (ii) to identify differentially expressed (DE) miRs between cachectic and non-cachectic cancer patients; (iii) to identify mRNA targets for the DE miRs to gain mechanistic insights; and (iv) to investigate if miRs show potential prognostic and predictive value...
January 6, 2017: Journal of Cachexia, Sarcopenia and Muscle
https://www.readbyqxmd.com/read/28058502/a-novel-loss-of-function-heterozygous-brca2-c-8946_8947delag-mutation-found-in-a-chinese-woman-with-family-history-of-breast-cancer
#19
Jing Ma, Jichun Yang, Wenjing Jian, Xianming Wang, Deyong Xiao, Wenjun Xia, Likuan Xiong, Duan Ma
INTRODUCTION: Breast cancer is the most frequent female malignancy worldwide. Among them, some cases have hereditary susceptibility in two leading genes, BRCA1 and BRCA2. Heterozygous germ line mutations in them are related with increased risk of breast, ovarian and other cancer, following autosomal dominant inheritance mode. METHODS AND RESULTS: For purpose of early finding, early diagnosis and early treatment, mutation detecting of BRCA1/2 genes was performed in unselected 300 breast or ovarian patients and unaffected women using next-generation sequencing and then confirmed by Sanger sequencing...
January 5, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28050010/benchmarking-of-whole-exome-sequencing-and-ad-hoc-designed-panels-for-genetic-testing-of-hereditary-cancer
#20
Lídia Feliubadaló, Raúl Tonda, Mireia Gausachs, Jean-Rémi Trotta, Elisabeth Castellanos, Adriana López-Doriga, Àlex Teulé, Eva Tornero, Jesús Del Valle, Bernat Gel, Marta Gut, Marta Pineda, Sara González, Mireia Menéndez, Matilde Navarro, Gabriel Capellá, Ivo Gut, Eduard Serra, Joan Brunet, Sergi Beltran, Conxi Lázaro
Next generation sequencing panels have been developed for hereditary cancer, although there is some debate about their cost-effectiveness compared to exome sequencing. The performance of two panels is compared to exome sequencing. Twenty-four patients were selected: ten with identified mutations (control set) and fourteen suspicious of hereditary cancer but with no mutation (discovery set). TruSight Cancer (94 genes) and a custom panel (122 genes) were assessed alongside exome sequencing. Eighty-three genes were targeted by the two panels and exome sequencing...
January 4, 2017: Scientific Reports
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