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Cell free tumour DNA

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https://www.readbyqxmd.com/read/29122359/prognostic-impact-of-rita-expression-in-patients-with-anal-squamous-cell-carcinoma-treated-with-chemoradiotherapy
#1
Franz Rödel, Kerstin Steinhäuser, Nina-Naomi Kreis, Alexandra Friemel, Daniel Martin, Ulrike Wieland, Margret Rave-Fränk, Panagiotis Balermpas, Emmanouil Fokas, Frank Louwen, Claus Rödel, Juping Yuan
BACKGROUND: RBP-J interacting and tubulin-associated protein (RITA) has been identified as a negative regulator of the Notch signalling pathway and its deregulation is involved in the pathogenesis of several tumour entities. RITA's impact on the response of anal squamous cell carcinoma (SCC) to anticancer treatment, however, remains elusive. MATERIALS AND METHODS: In our retrospective study immunohistochemical evaluation of RITA was performed on 140 pre-treatment specimens and was correlated with clinical and histopathologic characteristics and clinical endpoints cumulative incidence of local control (LC), distant recurrence (DC), disease-free survival (DFS) and overall survival (OS)...
November 6, 2017: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
https://www.readbyqxmd.com/read/29113230/squamous-cell-transformation-and-egfr-t790m-mutation-as-acquired-resistance-mechanisms-in-a-patient-with-lung-adenocarcinoma-treated-with-a-tyrosine-kinase-inhibitor-a-case-report
#2
Rossella Bruno, Agnese Proietti, Greta Alì, Gianfranco Puppo, Alessandro Ribechini, Antonio Chella, Gabriella Fontanini
The present case report describes the infrequent coexistence of squamous cell transformation and the epidermal growth factor receptor (EGFR) T790M mutation as resistance mechanisms to first line treatment with tyrosine kinase inhibitors. The patient was a 44-year-old female, diagnosed with a primitive advanced lung adenocarcinoma with bone metastases. The tumor was positive for the EGFR exon 19 deletion, therefore the patient was treated with afatinib (40 mg/day, orally) and radiotherapy for bone lesions. After 16 months, the patient developed resistance...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/29110846/egfr-mutation-prevalence-in-asia-pacific-and-russian-patients-with-advanced-nsclc-of-adenocarcinoma-and-non-adenocarcinoma-histology-the-ignite-study
#3
Baohui Han, Sergei Tjulandin, Koichi Hagiwara, Nicola Normanno, Laksmi Wulandari, Konstantin Laktionov, Achmad Hudoyo, Yong He, Yi-Ping Zhang, Meng-Zhao Wang, Chien Ying Liu, Marianne Ratcliffe, Rose McCormack, Martin Reck
OBJECTIVES: Limited understanding exists of epidermal growth factor receptor (EGFR) mutation frequency in less common subgroups of advanced non-small-cell lung cancer (aNSCLC) (e.g. squamous cell carcinoma [SCC]), and to what extent local practices exclude patients from EGFR testing based on their clinical characteristics. MATERIALS AND METHODS: IGNITE (non-comparative/-interventional; NCT01788163) was conducted in 90 centres (Asia-Pacific/Russia). Eligible patients: local/metastatic aNSCLC; chemotherapy-naïve, newly-diagnosed/recurrent disease after resection; ineligible for curative treatment...
November 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/29075515/characterisation-of-the-changing-genomic-landscape-of-metastatic-melanoma-using-cell-free-dna
#4
Anthony Cutts, Oliver Venn, Alexander Dilthey, Avinash Gupta, Dimitris Vavoulis, Helene Dreau, Mark Middleton, Gil McVean, Jenny C Taylor, Anna Schuh
Cancer is characterised by complex somatically acquired genetic aberrations that manifest as intra-tumour and inter-tumour genetic heterogeneity and can lead to treatment resistance. In this case study, we characterise the genome-wide somatic mutation dynamics in a metastatic melanoma patient during therapy using low-input (50 ng) PCR-free whole genome sequencing of cell-free DNA from pre-treatment and post-relapse blood samples. We identify de novo tumour-specific somatic mutations from cell-free DNA, while the sequence context of single nucleotide variants showed the characteristic UV-damage mutation signature of melanoma...
September 4, 2017: NPJ Genomic Medicine
https://www.readbyqxmd.com/read/29061138/the-evidence-base-for-circulating-tumour-dna-blood-based-biomarkers-for-the-early-detection-of-cancer-a-systematic-mapping-review
#5
Ian A Cree, Lesley Uttley, Helen Buckley Woods, Hugh Kikuchi, Anne Reiman, Susan Harnan, Becky L Whiteman, Sian Taylor Philips, Michael Messenger, Angela Cox, Dawn Teare, Orla Sheils, Jacqui Shaw
BACKGROUND: The presence of circulating cell-free DNA from tumours in blood (ctDNA) is of major importance to those interested in early cancer detection, as well as to those wishing to monitor tumour progression or diagnose the presence of activating mutations to guide treatment. In 2014, the UK Early Cancer Detection Consortium undertook a systematic mapping review of the literature to identify blood-based biomarkers with potential for the development of a non-invasive blood test for cancer screening, and which identified this as a major area of interest...
October 23, 2017: BMC Cancer
https://www.readbyqxmd.com/read/29022489/adar1-expression-is-associated-with-tumour-infiltrating-lymphocytes-in-triple-negative-breast-cancer
#6
In Hye Song, Young-Ae Kim, Sun-Hee Heo, In Ah Park, Miseon Lee, Won Seon Bang, Hye Seon Park, Gyungyub Gong, Hee Jin Lee
Tumours with a high mutation burden exhibit considerable neoantigens and tumour-infiltrating lymphocytes. RNA editing by ADAR1 is a source of changes in epitope. However, ADAR1 expression in cancer cells and tumour-infiltrating lymphocyte levels in triple-negative breast cancer have not been well evaluated. We immunohistochemically examined ADAR1 expression in 681 triple-negative breast cancer patients and analysed their clinicopathological characteristics. We also analysed basal-like tumours using The Cancer Genome Atlas data...
October 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28990231/ifi16-restoration-in-hepatocellular-carcinoma-induces-tumour-inhibition-via-activation-of-p53-signals-and-inflammasome
#7
Wei Lin, Zhiguang Zhao, Zhonglin Ni, Yaxin Zhao, Wenjun Du, Shijun Chen
OBJECTIVE: Interferon-inducible 16 (IFI16) is known to involve in p53-dependent tumour suppression and also the formation of inflammasome, which function, however, remains controversy during carcinogenesis as a pattern recognition receptor for tumour death-derived free DNA. In this study, we investigated the anti-tumour role of IFI16 in hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Hepatocellular carcinoma tissues (n = 20) and corresponding non-neoplastic tissues (n = 20) were collected to determine the expression of IFI16...
October 8, 2017: Cell Proliferation
https://www.readbyqxmd.com/read/28982739/discovery-of-methylated-circulating-dna-biomarkers-for-comprehensive-non-invasive-monitoring-of-treatment-response-in-metastatic-colorectal-cancer
#8
Ludovic Barault, Alessio Amatu, Giulia Siravegna, Agostino Ponzetti, Sebastian Moran, Andrea Cassingena, Benedetta Mussolin, Chiara Falcomatà, Alexandra M Binder, Carmen Cristiano, Daniele Oddo, Simonetta Guarrera, Carlotta Cancelliere, Sara Bustreo, Katia Bencardino, Sean Maden, Alice Vanzati, Patrizia Zavattari, Giuseppe Matullo, Mauro Truini, William M Grady, Patrizia Racca, Karin B Michels, Salvatore Siena, Manel Esteller, Alberto Bardelli, Andrea Sartore-Bianchi, Federica Di Nicolantonio
OBJECTIVE: Mutations in cell-free circulating DNA (cfDNA) have been studied for tracking disease relapse in colorectal cancer (CRC). This approach requires personalised assay design due to the lack of universally mutated genes. In contrast, early methylation alterations are restricted to defined genomic loci allowing comprehensive assay design for population studies. Our objective was to identify cancer-specific methylated biomarkers which could be measured longitudinally in cfDNA (liquid biopsy) to monitor therapeutic outcome in patients with metastatic CRC (mCRC)...
October 5, 2017: Gut
https://www.readbyqxmd.com/read/28972962/igf-1r-associates-with-adverse-outcomes-after-radical-radiotherapy-for-prostate-cancer
#9
Tamara Aleksic, Clare Verrill, Richard J Bryant, Cheng Han, Andrew Ross Worrall, Laurent Brureau, Stephane Larré, Geoff S Higgins, Fahad Fazal, Ahmad Sabbagh, Syed Haider, Francesca M Buffa, David Cole, Valentine M Macaulay
BACKGROUND: Activated type 1 insulin-like growth factor receptors (IGF-1Rs) undergo internalisation and nuclear translocation, promoting cell survival. We previously reported that IGF-1R inhibition delays DNA damage repair, sensitising prostate cancer cells to ionising radiation. Here we tested the clinical relevance of these findings. METHODS: We assessed associations between IGF-1R and clinical outcomes by immunohistochemistry in diagnostic biopsies of 136 men treated with 55-70 Gy external beam radiotherapy for prostate cancer, comparing results with publicly available transcriptional data in surgically treated patients...
October 3, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28967905/akt-overactivation-can-suppress-dna-repair-via-p70s6-kinase-dependent-downregulation-of-mre11
#10
D Piscitello, D Varshney, S Lilla, M G Vizioli, C Reid, V Gorbunova, A Seluanov, D A Gillespie, P D Adams
Deregulated AKT kinase activity due to PTEN deficiency in cancer cells contributes to oncogenesis by incompletely understood mechanisms. Here, we show that PTEN deletion in HCT116 and DLD1 colon carcinoma cells leads to suppression of CHK1 and CHK2 activation in response to irradiation, impaired G2 checkpoint proficiency and radiosensitization. These defects are associated with reduced expression of MRE11, RAD50 and NBS1, components of the apical MRE11/RAD50/NBS1 (MRN) DNA damage response complex. Consistent with reduced MRN complex function, PTEN-deficient cells fail to resect DNA double-strand breaks efficiently after irradiation and show greatly diminished proficiency for DNA repair via the error-free homologous recombination (HR) repair pathway...
October 2, 2017: Oncogene
https://www.readbyqxmd.com/read/28845132/cell-free-dna-in-non-small-cell-lung-cancer
#11
Vaida Gedvilaitė, Diana Schveigert, Saulius Cicėnas
Lung cancer is the leading cause of cancer-associated deaths worldwide. Surgery is the standard treatment for early-stage non-small cell lung cancer (NSCLC). Advances in the knowledge of the biology of non-small cell lung cancer have revealed molecular information used for systemic cancer therapy targeting metastatic disease, with an important impact on patients' overall survival (OS) and quality of life. However, a biopsy of overt metastases is an invasive procedure limited to certain locations and not easily acceptable in the clinic...
2017: Acta medica Lituanica
https://www.readbyqxmd.com/read/28841569/results-of-the-first-external-quality-assessment-scheme-eqa-for-isolation-and-analysis-of-circulating-tumour-dna-ctdna
#12
Verena Haselmann, Parviz Ahmad-Nejad, Wolf J Geilenkeuser, Angelika Duda, Merle Gabor, Romy Eichner, Simon Patton, Michael Neumaier
BACKGROUND: Circulating tumour DNA (ctDNA) is considered to have a high potential for future management of malignancies. This pilot external quality assessment (EQA) scheme aimed to address issues of analytical quality in this new area of laboratory diagnostics. METHODS: The EQA scheme consisted of three 2-mL EDTA-plasma samples spiked with fragmented genomic DNA with a mutant allele frequency ranging from 0% to 10% dedicated to the analysis of nine known sequence variations in KRAS codon 12/13 and of BRAF V600E...
August 25, 2017: Clinical Chemistry and Laboratory Medicine: CCLM
https://www.readbyqxmd.com/read/28827745/establishing-pnb-qpcr-for-quantifying-minimal-ctdna-concentrations-during-tumour-resection
#13
T Ehlert, S Tug, A Brahmer, V Neef, F Heid, C Werner, B Jansen-Winkeln, W Kneist, H Lang, I Gockel, P Simon
The analysis of blood plasma or serum as a non-invasive alternative to tissue biopsies is a much-pursued goal in cancer research. Various methods and approaches have been presented to determine a patient's tumour status, chances of survival, and response to therapy from serum or plasma samples. We established PNB-qPCR (Pooled, Nested, WT-Blocking qPCR), a highly specific nested qPCR with various modifications to detect and quantify minute amounts of circulating tumour DNA (ctDNA) from very limited blood plasma samples...
August 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28790338/statistical-analysis-of-mutant-allele-frequency-level-of-circulating-cell-free-dna-and-blood-cells-in-healthy-individuals
#14
Ligang Xia, Zhoufang Li, Bo Zhou, Geng Tian, Lidong Zeng, Hongyu Dai, Xiaohua Li, Chaoyu Liu, Shixin Lu, Feiyue Xu, Xiaonian Tu, Fang Deng, Yuancai Xie, Weiren Huang, Jiankui He
Cell-free DNA (cfDNA) in plasma has emerged as a potential important biomarker in clinical diagnostics, particularly in cancer. However, somatic mutations are also commonly found in healthy individuals, which interfere with the effectiveness for cancer diagnostics. This study examined the background somatic mutations in white blood cells (WBC) and cfDNA in healthy controls based on sequencing data from 821 non-cancer individuals and several cancer samples with the aim of understanding the patterns of mutations detected in cfDNA...
August 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28723472/human-prostate-tissue-derived-extracellular-matrix-as-a-model-of-prostate-microenvironment
#15
Walter Cazzaniga, Manuela Nebuloni, Erika Longhi, Irene Locatelli, Raffaele Allevi, Roberta Lucianò, Gelsomina Senatore, Eugenio Ventimiglia, Vito Cucchiara, Luca Genovese, Francesco Montorsi, Massimo Alfano, Andrea Salonia, Ilaria Cavarretta
BACKGROUND: Clinical experience highlights the wide heterogeneity of primary prostate cancer (PPCa), even when potentially related to the same grade and stage. Currently available prediction tools and biomarkers do not always allow for early recognition of PPCa aggressive phenotype, sometimes making it impossible to distinguish among men harbouring indolent tumours or life-threatening disease. OBJECTIVE: To establish a novel ex vivo/in vitro model suitable to estimate the invasive phenotype of PPCa cells (PPCaC)...
October 2016: European Urology Focus
https://www.readbyqxmd.com/read/28710679/new-phage-display-isolated-heptapeptide-recognizing-the-regulatory-carboxy-terminal-domain-of-human-tumour-protein-p53
#16
Sihem Ben Abid, Mouna Sahnoun, Ines Yacoubi-Hadj Amor, Salma Abdelmoula-Souissi, Hajer Hassairi, Raja Mokdad-Gargouri, Ali Gargouri
The transcription factor tumor protein p53 (P53) controls a variety of genes most involved in cell cycle and is at the origin of apoptosis when DNA is irreparably damaged. We planned to select novel tumor protein p53-interacting peptides through the screening of hepta-peptide phage-display libraries. For this aim, human tumor suppressor protein p53 was expressed in Escherichia coli as Glutathione S-transferase fusion and purified by affinity chromatography. The phage library was then screened on this immobilized protein target...
October 2017: Protein Journal
https://www.readbyqxmd.com/read/28692984/a-study-of-cell-free-dna-fragmentation-pattern-and-its-application-in-dna-sample-type-classification
#17
Shifu Chen, Ming Liu, Xiaoni Zhang, Renwen Long, Yixing Wang, Yue Han, Shiwei Zhang, Mingyan Xu, Jia Gu
Plasma cell-free DNA (cfDNA) has certain fragmentation patterns, which can bring non-random base content curves of the sequencing data's beginning cycles. We studied the patterns and found that we could determine whether a sample is cfDNA or not by just looking into the first 10 cycles of its base content curves. We analysed 3189 FastQ files, including 1442 cfDNA, 1234 genomic DNA, 507 FFPE tumour DNA and 6 urinary cfDNA. By deep analysing these data, we find the patterns are stable enough to distinguish cfDNA from other kinds of DNA samples...
July 4, 2017: IEEE/ACM Transactions on Computational Biology and Bioinformatics
https://www.readbyqxmd.com/read/28683468/correlation-between-circulating-mutant-dna-and-metabolic-tumour-burden-in-advanced-non-small-cell-lung-cancer-patients
#18
Anne Winther-Larsen, Christina Demuth, Joan Fledelius, Anne Tranberg Madsen, Karin Hjorthaug, Peter Meldgaard, Boe Sandahl Sorensen
BACKGROUND: Mutated circulating cell-free DNA (cfDNA) has been suggested as a surrogate marker of tumour burden and aggressiveness of disease. We examined the association between the level of plasma mutant cfDNA and metabolic tumour burden (MTB) measured by (18)F-fluoro-D-glucose positron emission tomography/computed tomography ((18)F-FDG PET/CT). Furthermore, the presence of mutant cfDNA was correlated with patient survival. METHODS: Forty-six advanced non-small cell lung cancer (NSCLC) patients were included...
August 22, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28647685/irtks-is-correlated-with-progression-and-survival-time-of-patients-with-gastric-cancer
#19
Li-Yu Huang, Xuefei Wang, Xiao-Fang Cui, He Li, Junjie Zhao, Chong-Chao Wu, Lingqiang Min, Zhicheng Zhou, Lixin Wan, Yu-Ping Wang, Chao Zhang, Wei-Qiang Gao, Yihong Sun, Ze-Guang Han
BACKGROUND AND OBJECTIVES: IRTKS functions as a novel regulator of tumour suppressor p53; however, the role of IRTKS in pathogenesis of gastric cancer is unclear. DESIGN: We used immunohistochemistry to detect IRTKS levels in 527 human gastric cancer specimens. We generated both IRTKS-deficient and p53-deficient mice to observe survival time of these mice and to isolate mouse embryonic fibroblasts (MEFs) for evaluating in vivo tumorigenicity. Co-immunoprecipitation was used to study the interaction among p53, MDM2 and IRTKS, as well as the ubiquitination of p53...
June 24, 2017: Gut
https://www.readbyqxmd.com/read/28641314/no-additional-prognostic-value-for-mre11-in-squamous-cell-carcinomas-of-the-anus-treated-with-chemo-radiotherapy
#20
Alexandra K Walker, Christiana Kartsonaki, Elena Collantes, Judith Nicholson, Duncan C Gilbert, Anne E Kiltie
BACKGROUND: The majority of anal cancers (84-95%) are driven by infection with human papillomavirus (HPV). HPV-positive tumours show significantly better responses to chemo-radiotherapy when compared with HPV-negative tumours. HPV infection is linked to alterations in DNA damage response proteins, including MRE11. MRE11 is a potential predictive biomarker for response to radiotherapy in muscle-invasive bladder cancer and may hold predictive power in other cancers. METHODS: Using a previously reported cohort, we evaluated the levels of MRE11 in anal cancer and assessed its predictive value in this disease...
July 25, 2017: British Journal of Cancer
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