Read by QxMD icon Read


Peiye Shen, Ying Jing, Ruiyun Zhang, Mei-Chun Cai, Pengfei Ma, Haige Chen, Guanglei Zhuang
Neuroendocrine bladder cancer is a relatively rare but often lethal malignancy, with cell of origin, oncogenomic architecture and standard treatment poorly defined. Here we performed comprehensive whole-genome and transcriptome sequencing on a unique cohort of genitourinary neuroendocrine neoplasms, mainly small cell carcinomas of the urinary bladder. The mutational landscape and signatures of neuroendocrine bladder cancer strikingly resembled those in conventional urothelial carcinoma, along with typically mixed histologies, supporting a common cellular origin...
March 14, 2018: Oncogene
Yuzhuo Wang, Cheng Wang, Jiahui Zhang, Meng Zhu, Xu Zhang, Zhihua Li, Juncheng Dai, Hongxia Ma, Zhibin Hu, Guangfu Jin, Hongbing Shen
Emerging evidence indicates that germline variations may interact with somatic events in carcinogenesis. However, the germline-somatic interaction in lung cancer remains largely unknown. We investigated whether lung cancer driver genes (CDGs) were more likely to locate within cancer susceptibility regions. Pathway analysis was performed to identify common pathways underlying CDGs and cancer susceptibility genes (CSGs). Next, we analyzed the associations between lung cancer risk SNPs and somatic alterations, including mutations and copy number alterations, in the level of genes, pathways, and overall burden of alterations...
March 1, 2018: International Journal of Cancer. Journal International du Cancer
Smita Nair, Adam Zlotnick
Cytidine deaminases inhibit replication of broad range of DNA viruses by deaminating cytidines on single stranded DNA to generate uracil. While several lines of evidence have revealed HBV genome editing by deamination, it is still unclear which nucleic acid intermediate of HBV is modified. Hepatitis B virus has a relaxed circular double-stranded DNA (rcDNA) genome that is reverse transcribed within virus cores from a RNA template. The HBV genome also persists as covalently closed circular DNA (cccDNA) in the nucleus of an infected cell...
February 28, 2018: Journal of Virology
Ikram Ullah, Govindasamy-Muralidharan Karthik, Amjad Alkodsi, Una Kjällquist, Gustav Stålhammar, John Lövrot, Nelson-Fuentes Martinez, Jens Lagergren, Sampsa Hautaniemi, Johan Hartman, Jonas Bergh
Metastatic breast cancers are still incurable. Characterizing the evolutionary landscape of these cancers, including the role of metastatic axillary lymph nodes (ALNs) in seeding distant organ metastasis, can provide a rational basis for effective treatments. Here, we have described the genomic analyses of the primary tumors and metastatic lesions from 99 samples obtained from 20 patients with breast cancer. Our evolutionary analyses revealed diverse spreading and seeding patterns that govern tumor progression...
February 26, 2018: Journal of Clinical Investigation
Yasuyuki Kanke, Akihiko Shimomura, Motonobu Saito, Takayuki Honda, Kouya Shiraishi, Yoko Shimada, Reiko Watanabe, Hiroshi Yoshida, Masayuki Yoshida, Chikako Shimizu, Kazuaki Takahashi, Hirohiko Totsuka, Hideaki Ogiwara, Sou Hirose, Koji Kono, Kenji Tamura, Aikou Okamoto, Takayuki Kinoshita, Tomoyasu Kato, Takashi Kohno
There has been little improvement in the prognosis for adolescent and young adult (AYA) tumor patients. Hence, there is an urgent need to understand the etiology of tumor development and identify actionable gene aberrations to improve prevention and therapy. Here, 76 sporadic tumors (48 breast, 22 ovarian, and six uterine) from 76 AYA females (age range, 25-39 years) were subjected to whole exome and RNA sequencing to determine their mutational signatures and actionable gene profiles. Two individuals with breast cancer (4...
January 19, 2018: Oncotarget
Alexander P Glaser, Damiano Fantini, Yiduo Wang, Yanni Yu, Kalen J Rimar, Joseph R Podojil, Stephen D Miller, Joshua J Meeks
APOBEC enzymes are responsible for a mutation signature (TCW>T/G) implicated in a wide variety of tumors. We explore the APOBEC mutational signature in bladder cancer and the relationship with specific mutations, molecular subtype, gene expression, and survival using sequencing data from The Cancer Genome Atlas (n = 395), Beijing Genomics Institute (n = 99), and Cancer Cell Line Encyclopedia. Tumors were split into "APOBEC-high" and "APOBEC-low" based on APOBEC enrichment. Patients with APOBEC-high tumors have better overall survival compared to those with APOBEC-low tumors (38...
January 12, 2018: Oncotarget
Wulfran Cacheux, Virginie Dangles-Marie, Etienne Rouleau, Julien Lazartigues, Elodie Girard, Adrien Briaux, Pascale Mariani, Sophie Richon, Sophie Vacher, Bruno Buecher, Marion Richard-Molard, Emmanuelle Jeannot, Nicolas Servant, Fereshteh Farkhondeh, Odette Mariani, Thomas Rio-Frio, Sergio Roman-Roman, Emmanuel Mitry, Ivan Bieche, Astrid Lièvre
Anal squamous cell carcinomas (ASCC) are rare tumours in humans. The etiological role of HPV infection is now well established but little is known about the molecular landscape and signalling pathways involved in the pathogenesis of this cancer. Here we report the results from a whole exome sequencing of a homogeneous group of 20 treatment-naive ASCC. A total of 2422 somatic single nucleotide variations (SNV) were found, with an overall moderate rate of somatic mutations per tumour (median: 105 relevant SNV per tumour) but a high mutational load in 3 tumours...
January 2, 2018: Oncotarget
Elisa Orecchini, Loredana Frassinelli, Silvia Galardi, Silvia Anna Ciafrè, Alessandro Michienzi
Long interspersed element-1 (LINE-1 or L1) retrotransposons represent the only functional family of autonomous transposable elements in humans and formed 17% of our genome. Even though most of the human L1 sequences are inactive, a limited number of copies per individual retain the ability to mobilize by a process termed retrotransposition. The ongoing L1 retrotransposition may result in insertional mutagenesis that could lead to negative consequences such as genetic disease and cancer. For this reason, cells have evolved several mechanisms of defense to restrict L1 activity...
February 2, 2018: Chromosome Research
Yingying Cao, Ruiyuan Cao, Yaowei Huang, Hongxia Zhou, Yuanhua Liu, Xuan Li, Wu Zhong, Pei Hao
BACKGROUND: RNA editing is an important mechanism that expands the diversity and complexity of genetic codes. The conversions of adenosine (A) to inosine (I) and cytosine (C) to uridine (U) are two prominent types of RNA editing in animals. The roles of RNA editing events have been implicated in important biological pathways. Cellular RNA editing activity in response to influenza A virus infection has not been fully characterized in human and avian hosts. This study was designed as a big data analysis to investigate the role and response of RNA editing in epithelial cells during the course of infection with various subtypes of influenza A viruses...
January 19, 2018: BMC Genomics
X C Li, M Y Wang, M Yang, H J Dai, B F Zhang, W Wang, X L Chu, X Wang, H Zheng, R F Niu, W Zhang, K X Chen
Background: Esophageal squamous cell carcinoma (ESCC) is often diagnosed at an advanced and incurable stage. Information on driver genes and prognosticators in ESCC remains incomplete. The objective was to elucidate significantly mutated genes (SMGs), mutational signatures, and prognosticators in ESCC. Patients and Methods: Three MutSig algorithms (i.e. MutSigCV, MutSigCL and MutSigFN) and "20/20+" ratio-metric were employed to identify SMGs. Nonnegative matrix factorization was used to decipher mutational signatures...
January 16, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Madison B Adolph, Robin P Love, Linda Chelico
The Apolipoprotein B mRNA editing complex (APOBEC) family of enzymes are single-stranded polynucleotide cytidine deaminases. These enzymes catalyze the deamination of cytidine in RNA or single-stranded DNA, which forms uracil. From this eleven member enzyme family in humans, the deamination of single-stranded DNA by the seven APOBEC3 family members are considered here. The APOBEC3 family has many roles such as, restricting endogenous and exogenous retrovirus replication and retrotransposon insertion events and reducing DNA-induced inflammation...
January 18, 2018: ACS Infectious Diseases
Kizuki Yuza, Masayuki Nagahashi, Satoshi Watanabe, Kazuaki Takabe, Toshifumi Wakai
Recent progress in cancer genome analysis using next-generation sequencing has revealed a high mutation burden in some tumors. The particularly high rate of somatic mutation in these tumors correlates with the generation of neo-antigens capable of eliciting an immune response. Identification of hypermutated tumors is therefore clinically valuable for selecting patients suitable for immunotherapy treatment. There are several known causes of hypermutation in tumors, such as ultraviolet light in melanoma, tobacco smoke in lung cancer, and excessive APOBEC (apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like) activity in breast and gastric cancer...
December 19, 2017: Oncotarget
S Venkatesan, R Rosenthal, N Kanu, N McGranahan, J Bartek, S A Quezada, J Hare, R S Harris, C Swanton
The APOBEC mutational signature has only recently been detected in a multitude of cancers through next-generation sequencing. In contrast, APOBEC has been a focus of virology research for over a decade. Many lessons learnt regarding APOBEC within virology are likely to be applicable to cancer. In this review, we explore the parallels between the role of APOBEC enzymes in HIV and cancer evolution. We discuss data supporting the role of APOBEC mutagenesis in creating HIV genome heterogeneity, drug resistance, and immune escape variants...
January 8, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Liqun Lei, Hongquan Chen, Wei Xue, Bei Yang, Bian Hu, Jia Wei, Lijie Wang, Yiqiang Cui, Wei Li, Jianying Wang, Lei Yan, Wanjing Shang, Jimin Gao, Jiahao Sha, Min Zhuang, Xingxu Huang, Bin Shen, Li Yang, Jia Chen
The APOBEC-AID family of cytidine deaminase prefers single-stranded nucleic acids for cytidine-to-uridine deamination. Single-stranded nucleic acids are commonly involved in the DNA repair system for breaks generated by CRISPR-Cas9. Here, we show in human cells that APOBEC3 can trigger cytidine deamination of single-stranded oligodeoxynucleotides, which ultimately results in base substitution mutations in genomic DNA through homology-directed repair (HDR) of Cas9-generated double-strand breaks. In addition, the APOBEC3-catalyzed deamination in genomic single-stranded DNA formed during the repair of Cas9 nickase-generated single-strand breaks in human cells can be further processed to yield mutations mainly involving insertions or deletions (indels)...
January 2018: Nature Structural & Molecular Biology
F Maura, M Petljak, M Lionetti, I Cifola, W Liang, E Pinatel, L B Alexandrov, A Fullam, I Martincorena, K J Dawson, N Angelopoulos, M K Samur, R Szalat, J Zamora, P Tarpey, H Davies, P Corradini, K C Anderson, S Minvielle, A Neri, H Avet-Loiseau, J Keats, P J Campbell, N C Munshi, N Bolli
No abstract text is available yet for this article.
December 6, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Sam Tilborghs, Jerome Corthouts, Yannick Verhoeven, David Arias, Christian Rolfo, Xuan Bich Trinh, Peter A van Dam
Background The Nuclear Factor kappaB (NF-kB) family consists of transcription factors that play a complex and essential role in the regulation of immune responses and inflammation. NF-kB has recently generated considerable interest as it has been implicated in human cancer initiation, progression and resistance to treatment. In the present comprehensive review the different aspects of NF-kB signaling in the carcinogenesis of cancer of the uterine cervix are discussed. NF-kB functions as part of a network, which determines the pattern of its effects on the expression of several other genes (such as crosstalks with reactive oxygen species, p53, STAT3 and miRNAS) and thus its function...
December 2017: Critical Reviews in Oncology/hematology
Matthew T Chang, Alexander V Penson, Neil B Desai, Nicholas D Socci, Ronglai Shen, Venkatraman Seshan, Ritika Kundra, Adam A Abeshouse, Agnes Viale, Eugene K Cha, Xueli Hao, Victor Reuter, Charles M Rudin, Bernard H Bochner, Jonathan E Rosenberg, Dean F Bajorin, Nikolaus Schultz, Michael F Berger, Gopa Iyer, David B Solit, Hikmat A Al-Ahmadie, Barry S Taylor
Background Small cell carcinoma of the bladder (SCCB) is a rare and aggressive neuroendocrine tumor with a dismal prognosis and limited treatment options. As SCCB is histologically indistinguishable from small cell lung cancer, a shared pathogenesis and cell of origin has been proposed. The aim of this study is to determine whether SCCBs arise from a pre-existent urothelial carcinoma or share a molecular pathogenesis in common with small cell lung cancer. Results We performed an integrative analysis of 61 SCCB tumors to identify histology- and organ-specific similarities and differences...
November 27, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Martina Heller, Elena-Sophie Prigge, Adam Kaczorowski, Magnus von Knebel Doeberitz, Markus Hohenfellner, Stefan Duensing
BACKGROUND: APOBECs (apolipoprotein B mRNA-editing catalytic polypeptides) are cytidine deaminases that have been implicated in the host defense against viruses by blocking viral replication. They have also been shown to play a role in genome hypermutation in several human cancers. An APOBEC3 hypermutation signature has been discovered in cervical cancer, which is intimately associated with infection by high-risk human papillomaviruses (HPVs). At the same time, HPV genomes themselves are subject to DNA editing by APOBECs...
November 23, 2017: Pathobiology: Journal of Immunopathology, Molecular and Cellular Biology
Margaret E Olson, Reuben S Harris, Daniel A Harki
Human DNA cytosine-to-uracil deaminases catalyze mutations in both pathogen and cellular genomes. APOBEC3D, APOBEC3F, APOBEC3G, and APOBEC3H restrict human immunodeficiency virus 1 (HIV-1) infection in cells deficient in the viral infectivity factor (Vif), and have the potential to catalyze sublethal levels of mutation in viral genomes in Vif-proficient cells. At least two APOBEC3 enzymes, and in particular APOBEC3B, are sources of somatic mutagenesis in cancer cells that drive tumor evolution and may manifest clinically as recurrence, metastasis, and/or therapy resistance...
November 14, 2017: Cell Chemical Biology
Liv B Gansmo, Paal Romundstad, Kristian Hveem, Lars Vatten, Serena Nik-Zainal, Per Eystein Lønning, Stian Knappskog
Activity of the APOBEC enzymes has been linked to specific mutational processes in human cancer genomes. A germline APOBEC3A/B deletion polymorphism is associated with APOBEC-dependent mutational signatures, and the deletion allele has been reported to confer an elevated risk of some cancers in Asian populations, while the results in European populations, so far, have been conflicting. We genotyped the APOBEC3A/B deletion polymorphism in a large population based sample consisting of 11,106 Caucasian (Norwegian) individuals, including 7,279 incident cancer cases (1,769 breast- , 1,360 lung-, 1,585 colon-, and 2,565 prostate cancer) and a control group of 3,827 matched individuals without cancer (1,918 females and 1,909 males) from the same population...
November 13, 2017: Carcinogenesis
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"