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https://www.readbyqxmd.com/read/28714863/dna-methylation-based-immune-response-signature-improves-patient-diagnosis-in-multiple-cancers
#1
Jana Jeschke, Martin Bizet, Christine Desmedt, Emilie Calonne, Sarah Dedeurwaerder, Soizic Garaud, Alexander Koch, Denis Larsimont, Roberto Salgado, Gert Van den Eynden, Karen Willard Gallo, Gianluca Bontempi, Matthieu Defrance, Christos Sotiriou, François Fuks
BACKGROUND: The tumor immune response is increasingly associated with better clinical outcomes in breast and other cancers. However, the evaluation of tumor-infiltrating lymphocytes (TILs) relies on histopathological measurements with limited accuracy and reproducibility. Here, we profiled DNA methylation markers to identify a methylation of TIL (MeTIL) signature that recapitulates TIL evaluations and their prognostic value for long-term outcomes in breast cancer (BC). METHODS: MeTIL signature scores were correlated with clinical endpoints reflecting overall or disease-free survival and a pathologic complete response to preoperative anthracycline therapy in 3 BC cohorts from the Jules Bordet Institute in Brussels and in other cancer types from The Cancer Genome Atlas...
July 17, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28685159/the-aurora-pilot-study-for-molecular-screening-of-patients-with-advanced-breast-cancer-a-study-of-the-breast-international-group
#2
Marion Maetens, David Brown, Alexandre Irrthum, Philippe Aftimos, Giuseppe Viale, Sibylle Loibl, Jean-François Laes, Peter J Campbell, Alastair Thompson, Javier Cortes, Sabine Seiler, Sara Vinnicombe, Mafalda Oliveira, Françoise Rothé, Yacine Bareche, Debora Fumagalli, Dimitrios Zardavas, Christine Desmedt, Martine Piccart, Sherene Loi, Christos Sotiriou
Several studies have demonstrated the feasibility of molecular screening of tumour samples for matching patients with cancer to targeted therapies. However, most of them have been carried out at institutional or national level. Herein, we report on the pilot phase of AURORA (NCT02102165), a European multinational collaborative molecular screening initiative for advanced breast cancer patients. Forty-one patients were prospectively enroled at four participating centres across Europe. Metastatic tumours were biopsied and profiled using an Ion Torrent sequencing platform at a central facility...
2017: NPJ Breast Cancer
https://www.readbyqxmd.com/read/28673354/the-footprint-of-the-ageing-stroma-in-older-patients-with-breast-cancer
#3
Barbara Brouwers, Debora Fumagalli, Sylvain Brohee, Sigrid Hatse, Olivier Govaere, Giuseppe Floris, Kathleen Van den Eynde, Yacine Bareche, Patrick Schöffski, Ann Smeets, Patrick Neven, Diether Lambrechts, Christos Sotiriou, Hans Wildiers
BACKGROUND: Tumours are not only composed of malignant cells but also consist of a stromal micro-environment, which has been shown to influence cancer cell behaviour. Because the ageing process induces accumulation of senescent cells in the body, this micro-environment is thought to be different in cancers occurring in old patients compared with younger patients. More specifically, senescence-related fibroblastic features, such as the senescence-associated secretory profile (SASP) and the induction of autophagy, are suspected to stimulate tumour growth and progression...
July 3, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28621322/reliability-of-tumor-infiltrating-lymphocyte-and-tertiary-lymphoid-structure-assessment-in-human-breast-cancer
#4
Laurence Buisseret, Christine Desmedt, Soizic Garaud, Marco Fornili, Xiaoxiao Wang, Gert Van den Eyden, Alexandre de Wind, Sebastien Duquenne, Anais Boisson, Celine Naveaux, Francoise Rothé, Sandrine Rorive, Christine Decaestecker, Denis Larsimont, Martine Piccart-Gebhart, Elia Biganzoli, Christos Sotiriou, Karen Willard-Gallo
The presence of tumor-infiltrating lymphocytes (TIL), reflecting host immune activity, is frequently correlated with better clinical outcomes, particularly in HER2-positive and triple-negative breast cancer. Recent findings suggest that organization of immune infiltrates in tertiary lymphoid structures also has a beneficial effect on survival. This study investigated inter- and intra-observer variation in TIL assessment using conventional hematoxylin-eosin versus immunohistochemical staining to identify immune cells...
June 16, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28614706/enhanced-rate-of-acquisition-of-point-mutations-in-mouse-intestinal-adenomas-compared-to-normal-tissue
#5
Natalia Lugli, Vasilis S Dionellis, Paloma Ordóñez-Morán, Irene Kamileri, Sotirios K Sotiriou, Joerg Huelsken, Thanos D Halazonetis
The most prevalent single-nucleotide substitution (SNS) found in cancers is a C-to-T substitution in the CpG motif. It has been proposed that many of these SNSs arise during organismal aging, prior to transformation of a normal cell into a precancerous/cancer cell. Here, we isolated single intestinal crypts derived from normal tissue or from adenomas of Apc(min/+) mice, expanded them minimally in vitro as organoids, and performed exome sequencing to identify point mutations that had been acquired in vivo at the single-cell level...
June 13, 2017: Cell Reports
https://www.readbyqxmd.com/read/28585536/erratum-phylogenetic-analysis-of-metastatic-progression-in-breast-cancer-using-somatic-mutations-and-copy-number-aberrations
#6
David Brown, Dominiek Smeets, Borbála Székely, Denis Larsimont, A Marcell Szász, Pierre-Yves Adnet, Françoise Rothé, Ghizlane Rouas, Zsófia I Nagy, Zsófia Faragó, Anna-Mária Tőkés, Magdolna Dank, Gyöngyvér Szentmártoni, Nóra Udvarhelyi, Gabriele Zoppoli, Lajos Pusztai, Martine Piccart, Janina Kulka, Diether Lambrechts, Christos Sotiriou, Christine Desmedt
This corrects the article DOI: 10.1038/ncomms14944.
June 6, 2017: Nature Communications
https://www.readbyqxmd.com/read/28566333/cdk4-phosphorylation-status-and-a-linked-gene-expression-profile-predict-sensitivity-to-palbociclib
#7
Eric Raspé, Katia Coulonval, Jaime M Pita, Sabine Paternot, Françoise Rothé, Laure Twyffels, Sylvain Brohée, Ligia Craciun, Denis Larsimont, Véronique Kruys, Flavienne Sandras, Isabelle Salmon, Steven Van Laere, Martine Piccart, Michail Ignatiadis, Christos Sotiriou, Pierre P Roger
Cyclin D-CDK4/6 are the first CDK complexes to be activated in the G1 phase in response to oncogenic pathways. The specific CDK4/6 inhibitor PD0332991 (palbociclib) was recently approved by the FDA and EMA for treatment of advanced ER-positive breast tumors. Unfortunately, no reliable predictive tools are available for identifying potentially responsive or insensitive tumors. We had shown that the activating T172 phosphorylation of CDK4 is the central rate-limiting event that initiates the cell cycle decision and signals the presence of active CDK4...
May 31, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28525810/tumor-infiltrating-lymphocytes-in-patients-with-her2-positive-breast-cancer-treated-with-neoadjuvant-chemotherapy-plus-trastuzumab-lapatinib-or-their-combination-a-meta-analysis-of-randomized-controlled-trials
#8
REVIEW
C Solinas, M Ceppi, M Lambertini, M Scartozzi, L Buisseret, S Garaud, D Fumagalli, E de Azambuja, R Salgado, C Sotiriou, K Willard-Gallo, M Ignatiadis
BACKGROUND: A relationship between baseline tumor-infiltrating lymphocytes (TIL) and outcomes has been described in HER2-positive breast cancer. Nevertheless, the magnitude of this association and whether this effect differs based on the type of anti-HER2 agent remain controversial. This meta-analysis investigated the association between baseline TIL and pathologic complete response (pCR) rates in HER2-positive breast cancer patients treated with neoadjuvant chemotherapy plus trastuzumab and lapatinib either alone or in combination...
June 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28515985/epidemiological-trends-in-skin-cancer
#9
Zoe Apalla, Aimilios Lallas, Elena Sotiriou, Elizabeth Lazaridou, Demetrios Ioannides
Skin cancer, including melanoma and non-melanoma skin cancer (NMSC), represents the most common type of malignancy in the white population. The incidence rate of melanoma is increasing worldwide, while the associated mortality remains stable, or is slightly decreasing. On the other hand, the incidence for NMSC varies widely, with the highest rates reported in Australia. In the current review, we highlight recent global trends in epidemiology of skin cancer. We discuss controversial issues raised in current epidemiological data, we analyze the most important risk factors associated with the development of melanoma and NMSC and the impact of skin cancer on health care services...
April 2017: Dermatology Practical & Conceptual
https://www.readbyqxmd.com/read/28429735/phylogenetic-analysis-of-metastatic-progression-in-breast-cancer-using-somatic-mutations-and-copy-number-aberrations
#10
David Brown, Dominiek Smeets, Borbála Székely, Denis Larsimont, A Marcell Szász, Pierre-Yves Adnet, Françoise Rothé, Ghizlane Rouas, Zsófia I Nagy, Zsófia Faragó, Anna-Mária Tőkés, Magdolna Dank, Gyöngyvér Szentmártoni, Nóra Udvarhelyi, Gabriele Zoppoli, Lajos Pusztai, Martine Piccart, Janina Kulka, Diether Lambrechts, Christos Sotiriou, Christine Desmedt
Several studies using genome-wide molecular techniques have reported various degrees of genetic heterogeneity between primary tumours and their distant metastases. However, it has been difficult to discern patterns of dissemination owing to the limited number of patients and available metastases. Here, we use phylogenetic techniques on data generated using whole-exome sequencing and copy number profiling of primary and multiple-matched metastatic tumours from ten autopsied patients to infer the evolutionary history of breast cancer progression...
April 20, 2017: Nature Communications
https://www.readbyqxmd.com/read/28400203/transcriptomic-and-genomic-features-of-invasive-lobular-breast-cancer
#11
REVIEW
Christine Desmedt, Gabriele Zoppoli, Christos Sotiriou, Roberto Salgado
Accounting for 10-15% of all breast neoplasms, invasive lobular breast cancer (ILC) is the second most common histological subtype of breast cancer after invasive ductal breast cancer (IDC). Understanding ILC biology, which differs from IDC in terms of clinical presentation, treatment response, relapse timing and patterns, is essential in order to adopt novel, disease-specific management strategies. While the contribution of the histological subtypes to tumour biology has been poorly investigated and acknowledged in the past, recently several major, independent efforts have led to the assembly and molecular characterization of well-annotated ILC case sets...
April 8, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28381415/her2-overexpressing-breast-cancers-amplify-fgfr-signaling-upon-acquisition-of-resistance-to-dual-therapeutic-blockade-of-her2
#12
Ariella B Hanker, Joan G Garrett, Monica Valeria Estrada, Preston D Moore, Paula G Ericsson, James P Koch, Emma Langley, Sharat Singh, Phillip S Kim, Garrett M Frampton, Eric M Sanford, Philip Owns, Jennifer Becker, M Reid Groseclose, Stephen Castellino, Heikki Joensuu, Jens Huober, Jan C Brase, Majjaj Samira, Sylvain Brohée, David Venet, David Brown, José Baselga, Martine Piccart, Christos Sotiriou, Carlos L Arteaga
Dual blockade of HER2 with trastuzumab and lapatinib or pertuzumab has been shown to be superior to single-agent trastuzumab. However, a significant fraction of HER2-overexpressing (HER2+) breast cancers escape from these drug combinations. In this study, we sought to discover the mechanisms of acquired resistance to the combination of lapatinib + trastuzumab.<br /><br />Experimental Design: HER2+ BT474 xenografts were treated with lapatinib + trastuzumab long-term until resistance developed. Potential mechanisms of acquired resistance were evaluated in lapatinib + trastuzumab-resistant (LTR) tumors by targeted capture next-generation sequencing...
April 5, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28329761/somatic-mutations-reveal-asymmetric-cellular-dynamics-in-the-early-human-embryo
#13
Young Seok Ju, Inigo Martincorena, Moritz Gerstung, Mia Petljak, Ludmil B Alexandrov, Raheleh Rahbari, David C Wedge, Helen R Davies, Manasa Ramakrishna, Anthony Fullam, Sancha Martin, Christopher Alder, Nikita Patel, Steve Gamble, Sarah O'Meara, Dilip D Giri, Torril Sauer, Sarah E Pinder, Colin A Purdie, Åke Borg, Henk Stunnenberg, Marc van de Vijver, Benita K T Tan, Carlos Caldas, Andrew Tutt, Naoto T Ueno, Laura J van 't Veer, John W M Martens, Christos Sotiriou, Stian Knappskog, Paul N Span, Sunil R Lakhani, Jórunn Erla Eyfjörd, Anne-Lise Børresen-Dale, Andrea Richardson, Alastair M Thompson, Alain Viari, Matthew E Hurles, Serena Nik-Zainal, Peter J Campbell, Michael R Stratton
Somatic cells acquire mutations throughout the course of an individual's life. Mutations occurring early in embryogenesis are often present in a substantial proportion of, but not all, cells in postnatal humans and thus have particular characteristics and effects. Depending on their location in the genome and the proportion of cells they are present in, these mosaic mutations can cause a wide range of genetic disease syndromes and predispose carriers to cancer. They have a high chance of being transmitted to offspring as de novo germline mutations and, in principle, can provide insights into early human embryonic cell lineages and their contributions to adult tissues...
March 30, 2017: Nature
https://www.readbyqxmd.com/read/28288110/hrdetect-is-a-predictor-of-brca1-and-brca2-deficiency-based-on-mutational-signatures
#14
Helen Davies, Dominik Glodzik, Sandro Morganella, Lucy R Yates, Johan Staaf, Xueqing Zou, Manasa Ramakrishna, Sancha Martin, Sandrine Boyault, Anieta M Sieuwerts, Peter T Simpson, Tari A King, Keiran Raine, Jorunn E Eyfjord, Gu Kong, Åke Borg, Ewan Birney, Hendrik G Stunnenberg, Marc J van de Vijver, Anne-Lise Børresen-Dale, John W M Martens, Paul N Span, Sunil R Lakhani, Anne Vincent-Salomon, Christos Sotiriou, Andrew Tutt, Alastair M Thompson, Steven Van Laere, Andrea L Richardson, Alain Viari, Peter J Campbell, Michael R Stratton, Serena Nik-Zainal
Approximately 1-5% of breast cancers are attributed to inherited mutations in BRCA1 or BRCA2 and are selectively sensitive to poly(ADP-ribose) polymerase (PARP) inhibitors. In other cancer types, germline and/or somatic mutations in BRCA1 and/or BRCA2 (BRCA1/BRCA2) also confer selective sensitivity to PARP inhibitors. Thus, assays to detect BRCA1/BRCA2-deficient tumors have been sought. Recently, somatic substitution, insertion/deletion and rearrangement patterns, or 'mutational signatures', were associated with BRCA1/BRCA2 dysfunction...
April 2017: Nature Medicine
https://www.readbyqxmd.com/read/28222901/pharmacotherapy-in-smoking-cessation-corticotropin-releasing-factor-receptors-as-emerging-intervention-targets
#15
REVIEW
Ioannis Sotiriou, Kleanthi Chalkiadaki, Christos Nikolaidis, Kyriaki Sidiropoulou, Ekaterini Chatzaki
Smoking represents perhaps the single most important health risk factor and a global contributor to mortality that can unquestionably be prevented. Smoking is responsible for many diseases, including various types of cancer, chronic obstructive pulmonary disease, coronary heart disease, peripheral vascular disease and peptic ulcer, while it adversely affects fetal formation and development. Since smoking habit duration is a critical factor for mortality, the goal of treatment should be its timely cessation and relapse prevention...
February 14, 2017: Neuropeptides
https://www.readbyqxmd.com/read/28222225/daylight-photodynamic-therapy-vs-conventional-photodynamic-therapy-as-skin-cancer-preventive-treatment-in-patients-with-face-and-scalp-cancerization-an-intra-individual-comparison-study
#16
Elena Sotiriou, Demetrios Ioannides, Fotini Vrani, Elizabeth Lazaridou, Efstratios Vakirlis, Aimilios Lallas, Zoe Apalla
BACKGROUND: Individuals with medical history of non-melanoma skin cancers (NMSCs) usually develop multiple and/or recurrent malignant lesions around the site of the primary neoplasm. The latter represents the clinical expression of the "field cancerization" theory; supporting the presence of multiple malignant clones of dysplastic keratinocytes over the entire epithelium that potentially can progress into clinical lesions. Taking into consideration that the burden of NMSCs on public health and health-care cost is high, adequate control of recurrences and management of field change is challenging...
February 21, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/28197375/tumor-infiltrating-lymphocyte-composition-organization-and-pd-1-pd-l1-expression-are-linked-in-breast-cancer
#17
Laurence Buisseret, Soizic Garaud, Alexandre de Wind, Gert Van den Eynden, Anais Boisson, Cinzia Solinas, Chunyan Gu-Trantien, Céline Naveaux, Jean-Nicolas Lodewyckx, Hugues Duvillier, Ligia Craciun, Isabelle Veys, Denis Larsimont, Martine Piccart-Gebhart, John Stagg, Christos Sotiriou, Karen Willard-Gallo
The clinical relevance of tumor-infiltrating lymphocytes (TIL) in breast cancer (BC) has been clearly established by their demonstrated correlation with long-term positive outcomes. Nevertheless, the relationship between protective immunity, observed in some patients, and critical features of the infiltrate remains unresolved. This study examined TIL density, composition and organization together with PD-1 and PD-L1 expression in freshly collected and paraffin-embedded tissues from 125 patients with invasive primary BC...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28151718/the-prognostic-role-of-androgen-receptor-in-patients-with-early-stage-breast-cancer-a-meta-analysis-of-clinical-and-gene-expression-data
#18
Ivana Bozovic-Spasojevic, Dimitrios Zardavas, Sylvain Brohée, Lieveke Ameye, Debora Fumagalli, Felipe Ades, Evandro de Azambuja, Yacine Bareche, Martine Piccart, Marianne Paesmans, Christos Sotiriou
Purpose: Androgen receptor (AR) expression has been observed in about 70% of patients with breast cancer, but its prognostic role remains uncertain.Experimental Design: To assess the prognostic role of AR expression in early-stage breast cancer, we performed a meta-analysis of studies that evaluated the impact of AR at the protein and gene expression level on disease-free survival (DFS) and/or overall survival (OS). Eligible studies were identified by systematic review of electronic databases using the MeSH-terms "breast neoplasm" and "androgen receptor" and were selected after a qualitative assessment based on the REMARK criteria...
November 9, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28031185/metadcn-meta-analysis-framework-for-differential-co-expression-network-detection-with-an-application-in-breast-cancer
#19
Li Zhu, Ying Ding, Cho-Yi Chen, Lin Wang, Zhiguang Huo, SungHwan Kim, Christos Sotiriou, Steffi Oesterreich, George C Tseng
Motivation: Gene co-expression network analysis from transcriptomic studies can elucidate gene-gene interactions and regulatory mechanisms. Differential co-expression analysis helps further detect alterations of regulatory activities in case/control comparison. Co-expression networks estimated from single transcriptomic study is often unstable and not generalizable due to cohort bias and limited sample size. With the rapid accumulation of publicly available transcriptomic studies, co-expression analysis combining multiple transcriptomic studies can provide more accurate and robust results...
April 15, 2017: Bioinformatics
https://www.readbyqxmd.com/read/27984746/mammalian-rad52-functions-in-break-induced-replication-repair-of-collapsed-dna-replication-forks
#20
Sotirios K Sotiriou, Irene Kamileri, Natalia Lugli, Konstantinos Evangelou, Caterina Da-Ré, Florian Huber, Laura Padayachy, Sebastien Tardy, Noemie L Nicati, Samia Barriot, Fena Ochs, Claudia Lukas, Jiri Lukas, Vassilis G Gorgoulis, Leonardo Scapozza, Thanos D Halazonetis
Human cancers are characterized by the presence of oncogene-induced DNA replication stress (DRS), making them dependent on repair pathways such as break-induced replication (BIR) for damaged DNA replication forks. To better understand BIR, we performed a targeted siRNA screen for genes whose depletion inhibited G1 to S phase progression when oncogenic cyclin E was overexpressed. RAD52, a gene dispensable for normal development in mice, was among the top hits. In cells in which fork collapse was induced by oncogenes or chemicals, the Rad52 protein localized to DRS foci...
December 15, 2016: Molecular Cell
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