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Tumour heterogeneity

Yu Liu, Jianjun Zhang, Lin Li, Guangliang Yin, Jianhua Zhang, Shan Zheng, Hannah Cheung, Ning Wu, Ning Lu, Xizeng Mao, Longhai Yang, Jiexin Zhang, Li Zhang, Sahil Seth, Huang Chen, Xingzhi Song, Kan Liu, Yongqiang Xie, Lina Zhou, Chuanduo Zhao, Naijun Han, Wenting Chen, Susu Zhang, Longyun Chen, Wenjun Cai, Lin Li, Miaozhong Shen, Ningzhi Xu, Shujun Cheng, Huanming Yang, J Jack Lee, Arlene Correa, Junya Fujimoto, Carmen Behrens, Chi-Wan Chow, William N William, John V Heymach, Waun Ki Hong, Stephen Swisher, Ignacio I Wistuba, Jun Wang, Dongmei Lin, Xiangyang Liu, P Andrew Futreal, Yanning Gao
Multiple synchronous lung cancers (MSLCs) present a clinical dilemma as to whether individual tumours represent intrapulmonary metastases or independent tumours. In this study we analyse genomic profiles of 15 lung adenocarcinomas and one regional lymph node metastasis from 6 patients with MSLC. All 15 lung tumours demonstrate distinct genomic profiles, suggesting all are independent primary tumours, which are consistent with comprehensive histopathological assessment in 5 of the 6 patients. Lung tumours of the same individuals are no more similar to each other than are lung adenocarcinomas of different patients from TCGA cohort matched for tumour size and smoking status...
October 21, 2016: Nature Communications
Sara S Franco, Karolina Szczesna, Maria S Iliou, Mohammed Al-Qahtani, Ali Mobasheri, Julianna Kobolák, András Dinnyés
Cancer cells, stem cells and cancer stem cells have for a long time played a significant role in the biomedical sciences. Though cancer therapy is more effective than it was a few years ago, the truth is that still none of the current non-surgical treatments can cure cancer effectively. The reason could be due to the subpopulation called "cancer stem cells" (CSCs), being defined as those cells within a tumour that have properties of stem cells: self-renewal and the ability for differentiation into multiple cell types that occur in tumours...
September 30, 2016: BMC Cancer
Paul M Simkin, Natalie Yang, Alpha Tsui, Renate M Kalnins, Greg Fitt, Frank Gaillard
INTRODUCTION: Gemistocytic astrocytoma is the second most common subtype of World Health Organization grade 2 astrocytoma, but has a worse prognosis than other grade 2 lesions. We aim to describe the MR imaging features of histopathologically proven gemistocytic tumours. METHODS: Ethics approval was obtained from both institutions. Patient consent was not required for this retrospective study. We reviewed MR imaging findings of 16 consecutive cases of histopathologically proven gemistocytic astrocytoma and anaplastic astrocytoma with gemistocytic features...
October 21, 2016: Journal of Medical Imaging and Radiation Oncology
E Matyja, W Grajkowska, K Stępień, E Naganska
Pilocytic astrocytomas (PAs) are the most frequent primary astroglial tumours affecting children and adolescents. They occur sporadically or in association with a genetically determined syndrome - neurofibromatosis type 1. Classic PA usually manifests as a well-circumscribed, often cystic, slowly growing tumour, which corresponds to WHO grade I. The majority of pilocytic tumours arise along the neuraxis, predominantly in the cerebellum. They are associated with favourable long-term outcome or spontaneous regression, even after incomplete resection...
2016: Folia Neuropathologica
Mustapha Abubakar, Nick Orr, Frances Daley, Penny Coulson, H Raza Ali, Fiona Blows, Javier Benitez, Roger Milne, Herman Brenner, Christa Stegmaier, Arto Mannermaa, Jenny Chang-Claude, Anja Rudolph, Peter Sinn, Fergus J Couch, Peter Devilee, Rob A E M Tollenaar, Caroline Seynaeve, Jonine Figueroa, Mark E Sherman, Jolanta Lissowska, Stephen Hewitt, Diana Eccles, Maartje J Hooning, Antoinette Hollestelle, John W M Martens, Carolien H M van Deurzen, kConFab Investigators, Manjeet K Bolla, Qin Wang, Michael Jones, Minouk Schoemaker, Jelle Wesseling, Flora E van Leeuwen, Laura Van 't Veer, Douglas Easton, Anthony J Swerdlow, Mitch Dowsett, Paul D Pharoah, Marjanka K Schmidt, Montserrat Garcia-Closas
BACKGROUND: The value of KI67 in breast cancer prognostication has been questioned due to concerns on the analytical validity of visual KI67 assessment and methodological limitations of published studies. Here, we investigate the prognostic value of automated KI67 scoring in a large, multicentre study, and compare this with pathologists' visual scores available in a subset of patients. METHODS: We utilised 143 tissue microarrays containing 15,313 tumour tissue cores from 8088 breast cancer patients in 10 collaborating studies...
October 18, 2016: Breast Cancer Research: BCR
Darren Rodenhizer, Dan Cojocari, Bradly G Wouters, Alison P McGuigan
The tumour microenvironment is heterogeneous and consists of multiple cell types, variable extracellular matrix (ECM) composition, and contains cell-defined gradients of small molecules, oxygen, nutrients and waste. Emerging in vitro cell culture systems that attempt to replicate these features often fail to incorporate design strategies to facilitate efficient data collection and stratification. The tissue roll for analysis of cellular environment and response (TRACER) is a novel strategy to assemble layered, three-dimensional tumours with cell-defined, graded heterogeneous microenvironments that also facilitates cellular separation and stratification of data from different cell populations from specific microenvironments...
October 18, 2016: Biofabrication
Daniel Nava Rodrigues, Gunther Boysen, Semini Sumanasuriya, George Seed, Angelo M De Marzo, Johann de Bono
Prostate cancer (PCa) is a clinically heterogeneous disease and current treatment strategies are based largely on anatomical and pathological parameters. In the recent past, several DNA sequencing studies of primary and advanced PCa have revealed recurrent patterns of genomic aberrations that expose mechanisms of resistance to available therapies and potential new drug targets. Suppression of androgen receptor (AR) signalling is the cornerstone of advanced prostate cancer treatment. Genomic aberrations of the androgen receptor or alternative splicing of its mRNA are increasingly recognized as biomarkers of resistance to AR-targeted therapy such as abiraterone or enzalutamide...
October 18, 2016: Journal of Pathology
M Maddah, S Harsini, V Ziaee, M H Moradinejad, A Rezaei, S Zoghi, M Sadr, Y Aghighi, N Rezaei
Juvenile idiopathic arthritis (JIA) is a heterogeneous autoimmune disorder of unknown origin. As proinflammatory cytokines are known to contribute towards the pathogenesis of JIA, this case-control study was performed to examine the associations of certain single nucleotide polymorphisms (SNPs) of tumour necrosis factor-α (TNF-α) gene. Fifty-three patients with JIA participated in this study as patients group and compared with 137 healthy unrelated controls. Genotyping was performed for TNF-α gene at positions -308 and -238, using polymerase chain reaction with sequence-specific primers method...
October 18, 2016: International Journal of Immunogenetics
Antonino Carbone, Annunziata Gloghini, Arnaldo Caruso, Paolo De Paoli, Riccardo Dolcetti
The pathogenesis of classical Hodgkin lymphoma (cHL) is still enigmatic, largely because its tumor cells, the so-called Hodgkin and Reed-Stenberg (HRS) cells, invariably reside in a prominent reactive microenvironment, are rare and therefore difficult to analyze. On the other hand, the broadly investigated cHL-derived cell lines are not unequivocally considered as suitable and representative models for this puzzling disease. Based on current knowledge, it appears that the cross talk between the tumour cells and the reactive infiltrate of the microenvironment is complex and that multiple mechanisms occur, making cHL a very heterogeneous disease...
October 17, 2016: International Journal of Cancer. Journal International du Cancer
Jezkova Eva, Kajo Karol, Zubor Pavol, Grendar Marian, Malicherova Bibiana, Mendelova Andrea, Dokus Karol, Lasabova Zora, Plank Lukas, Danko Jan
Breast cancer is a heterogeneous disease with very different responses to therapy and different length of survival. In many cases, however, the determination of the stage and histopathological characteristics of breast cancer is insufficient to predict prognosis and response to treatment for the vast heterogeneity of the disease. To understand the molecular signature of subtypes of breast cancer, we attempted to identify the methylation status of key tumour suppressor gene Ras association (RalGDS/AF-6) domain family member 1 isoform a (RASSF1A) and a member of the paired-like homeodomain transcription factor family which functions in left-right asymmetry development (PITX2) and to correlate results with known clinicopathological features of breast cancer...
October 15, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Jan Franko, Qian Shi, Jeffrey P Meyers, Timothy S Maughan, Richard A Adams, Matthew T Seymour, Leonard Saltz, Cornelis J A Punt, Miriam Koopman, Christophe Tournigand, Niall C Tebbutt, Eduardo Diaz-Rubio, John Souglakos, Alfredo Falcone, Benoist Chibaudel, Volker Heinemann, Joseph Moen, Aimery De Gramont, Daniel J Sargent, Axel Grothey
BACKGROUND: Patients with peritoneal metastatic colorectal cancer have reduced overall survival compared with patients with metastatic colorectal cancer without peritoneal involvement. Here we further investigated the effect of the number and location of metastases in patients receiving first-line systemic chemotherapy. METHODS: We analysed individual patient data for previously untreated patients enrolled in 14 phase 3 randomised trials done between 1997 and 2008...
October 12, 2016: Lancet Oncology
Ottó Dócs, Katalin Hegyi, Attila Mokánszky, Anikó Mónusné, Lívia Beke, Csilla András, Judit Bedekovics, Gábor Méhes
Mutation rates determined by allele-specific PCR can be highly different in KRAS exon 2 mutant colorectal carcinoma (CRC) samples suggesting intratumoural heterogeneity. To address the effect of KRAS gene copy number on the relative mutant allele frequency the KRAS locus was individually quantified following FISH analysis in 36 cases. We observed, that mutant KRAS status was associated with an elevated KRAS locus number (2.36 ± 0.42 vs 2.63 ± 0.75; p = 0.037) reflecting an increased aneuploidy status but no true amplification of the locus...
October 15, 2016: Pathology Oncology Research: POR
E Sala, E Mema, Y Himoto, H Veeraraghavan, J D Brenton, A Snyder, B Weigelt, H A Vargas
Tumour heterogeneity in cancers has been observed at the histological and genetic levels, and increased levels of intra-tumour genetic heterogeneity have been reported to be associated with adverse clinical outcomes. This review provides an overview of radiomics, radiogenomics, and habitat imaging, and examines the use of these newly emergent fields in assessing tumour heterogeneity and its implications. It reviews the potential value of radiomics and radiogenomics in assisting in the diagnosis of cancer disease and determining cancer aggressiveness...
October 11, 2016: Clinical Radiology
Youn Jin Choi, Je-Keun Rhee, Soo Young Hur, Min Sung Kim, Sung Hak Lee, Yeun-Jun Chung, Tae-Min Kim, Sug Hyung Lee
Intra-individual tumoural heterogeneity (ITH) is a hallmark of solid tumours and impedes accurate genomic diagnosis and selection of proper therapy. The purpose of this study was to identify ITH of ovarian high-grade serous carcinomas (OSCs) and to determine the utility of ascitic cancer cells as a resource for mutation profiling in spite of ITH. We performed whole-exome sequencing, copy number profiling, and DNA methylation profiling of four OSC genomes using multiregional biopsy from 13 intra-ovarian lesions, 12 extra-ovarian tumour lesions (omentum/peritoneum), and ascitic cells...
October 14, 2016: Journal of Pathology
A Collarino, R A Valdés Olmos, A F van der Hoeven, L M Pereira Arias-Bouda
PURPOSE: This review aims to discuss the methodological aspects of dedicated molecular breast imaging (MBI) using (99m)Tc-sestamibi as radiotracer to guide biopsy of occult or unclear breast lesions on mammography (MG) and ultrasound (US) that are suspicious on MBI (BI-RADS criteria 4 and 5), including its advantages, limitations and future clinical applications. METHODS: Literature search was performed using the PubMed/MEDLINE database and "(99m)Tc-sestamibi", "biopsy" and "breast cancer" as keywords...
2016: Clinical and Translational Imaging: Reviews in Nuclear Medicine and Molecular Imaging
Andrzej Świerniak, Michał Krześlak
BACKGROUND: Evolutionary game theory (EGT) has been widely used to simulate tumour processes. In almost all studies on EGT models analysis is limited to two or three phenotypes. Our model contains four main phenotypes. Moreover, in a standard approach only heterogeneity of populations is studied, while cancer cells remain homogeneous. A multilayer approach proposed in this paper enables to study heterogeneity of single cells. METHOD: In the extended model presented in this paper we consider four strategies (phenotypes) that can arise by mutations...
October 13, 2016: Biology Direct
John R Benson, Ismail Jatoi, Masakazu Toi
The heterogeneous nature of ductal carcinoma in situ has been emphasised by data for breast-cancer screening that show substantial increases in the detection of early-stage non-invasive breast cancer but no noteworthy change in the incidence of invasive and distant metastatic disease. Indolent non-progressive forms of ductal carcinoma in situ are managed according to similar surgical strategies as high-risk disease, with extent of resection dictated by radiological and pathological estimates of tumour dimensions...
October 2016: Lancet Oncology
E Vandendriessche, G Van De Putte, R Van Den Broecke, Etm De Jonge
AIM: Intra and inter tumour heterogeneity is a known feature in cancer because tumour cells undergo changes at genetic and epigenetic level as they spread from their primary tumour site. Adjuvant treatment protocols in breast cancer are currently based on the biological characteristics of the primary tumour, which in most cases has been removed surgically. Considering tumour heterogeneity in metastases we examined the present status of knowledge regarding measurable differences in tumour profiling between the primary breast tumour and its synchronous axillary lymph node metastases (ALNM) and if so whether adjuvant therapy directed towards the tumour characteristics of the ALNM instead of those of the primary tumour is more effective...
December 28, 2015: Facts, Views & Vision in ObGyn
Marco E Allaix, Edgar J B Furnée, Massimiliano Mistrangelo, Alberto Arezzo, Mario Morino
Laparoscopic resection for colon and rectal cancer is associated with quicker return of bowel function, reduced postoperative morbidity rates and shorter length of hospital stay compared to open surgery, with no differences in long-term survival. Conversion to open surgery is reported in up to 30% of patients enrolled in randomized control trials comparing open and laparoscopic colorectal resection for cancer. In this review, reasons for conversion are anatomical-related factors, disease-related-factors and surgeon-related factors...
October 7, 2016: World Journal of Gastroenterology: WJG
Tamás Sticz, Anna Molnár, Ágnes Márk, Melinda Hajdu, Noémi Nagy, Gyula Végső, Tamás Micsik, László Kopper, Anna Sebestyén
AIMS: Tumour heterogeneity and altered activation of signalling pathways play important roles in therapy resistance. The PI3K/Akt/mTOR signalling network is a well-known regulator of several functions that contribute to tumour growth. mTOR exists in two functionally different multiprotein complexes. We aimed to determine mTOR activity-related proteins in clinically followed, conventionally treated colon carcinomas and to analyse the correlation between clinical data and mTORC1 and mTORC2 activity...
October 11, 2016: Journal of Clinical Pathology
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