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intratumor heterogeneity

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https://www.readbyqxmd.com/read/27904775/disease-evolution-and-heterogeneity-in-bilateral-breast-cancer
#1
Elena Fountzilas, Vassiliki Kotoula, Flora Zagouri, Eleni Giannoulatou, George Kouvatseas, George Pentheroudakis, Triantafyllia Koletsa, Mattheos Bobos, Kyriaki Papadopoulou, Epaminontas Samantas, Efterpi Demiri, Spyros Miliaras, Christos Christodoulou, Sofia Chrisafi, Evangelia Razis, Florentia Fostira, Dimitrios Pectasides, George Zografos, George Fountzilas
Bilateral breast cancers (BBC) are currently treated as independent tumors arising in the same patient. Herein, we investigated whether BBC indeed evolve independently at the genomic level. We examined paired targeted next generation sequencing genotypes from 155 paraffin tumors corresponding to 76 BBC patients (75 women and one man; 52 concurrent and 24 metachronous), for coding mutations (amino acid changing, minor allele frequency <0.1%) and single nucleotide polymorphism (SNP) zygosity. Germline genotypes were available for 29 patients...
2016: American Journal of Cancer Research
https://www.readbyqxmd.com/read/27903987/mapping-heterogeneity-in-patient-derived-melanoma-cultures-by-single-cell-rna-seq
#2
Tobias Gerber, Edith Willscher, Henry Loeffler-Wirth, Lydia Hopp, Dirk Schadendorf, Manfred Schartl, Ulf Anderegg, Gray Camp, Barbara Treutlein, Hans Binder, Manfred Kunz
Recent technological advances in single-cell genomics make it possible to analyze cellular heterogeneity of tumor samples. Here, we applied single-cell RNA-seq to measure the transcriptomes of 307 single cells cultured from three biopsies of three different patients with a BRAF/NRAS wild type, BRAF mutant/NRAS wild type and BRAF wild type/NRAS mutant melanoma metastasis, respectively. Analysis based on self-organizing maps identified sub-populations defined by multiple gene expression modules involved in proliferation, oxidative phosphorylation, pigmentation and cellular stroma...
November 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27899233/clear-cell-type-a-and-b-molecular-subtypes-in-metastatic-clear-cell-renal-cell-carcinoma-tumor-heterogeneity-and-aggressiveness
#3
Daniel J Serie, Richard W Joseph, John C Cheville, Thai H Ho, Mansi Parasramka, Tracy Hilton, R Houston Thompson, Bradley C Leibovich, Alexander S Parker, Jeanette E Eckel-Passow
BACKGROUND: Intratumor molecular heterogeneity has been reported for primary clear cell renal cell carcinoma (ccRCC) tumors; however, heterogeneity in metastatic ccRCC tumors has not been explored. OBJECTIVE: To evaluate intra- and intertumor molecular heterogeneity in resected metastatic ccRCC tumors. DESIGN, SETTING, AND PARTICIPANTS: We identified 111 patients who had tissue available from their primary tumor and at least one metastasis...
November 26, 2016: European Urology
https://www.readbyqxmd.com/read/27883053/measuring-intratumor-heterogeneity-by-network-entropy-using-rna-seq-data
#4
Youngjune Park, Sangsoo Lim, Jin-Wu Nam, Sun Kim
Intratumor heterogeneity (ITH) is observed at different stages of tumor progression, metastasis and reouccurence, which can be important for clinical applications. We used RNA-sequencing data from tumor samples, and measured the level of ITH in terms of biological network states. To model complex relationships among genes, we used a protein interaction network to consider gene-gene dependency. ITH was measured by using an entropy-based distance metric between two networks, nJSD, with Jensen-Shannon Divergence (JSD)...
November 24, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27870730/cutaneous-sebaceous-lesions-in-a-patient-with-mutyh-associated-polyposis-mimicking-muir-torre-syndrome
#5
Denisa Kacerovska, Lubomir Drlik, Lenka Slezakova, Michal Michal, Jan Stehlik, Monika Sedivcova, Ladislav Hadravsky, Dmitry V Kazakov
A 76-year-old white male with a history of adenocarcinoma of the rectosigmoideum and multiple colonic polyps removed at the age of 38 and 39 years by an abdominoperitoneal amputation and total colectomy, respectively, presented with multiple whitish and yellowish papules on the face and a verrucous lesion on the trunk. The lesions were surgically removed during the next 3 years and a total of 13 lesions were investigated histologically. The diagnoses included 11 sebaceous adenomas, 1 low-grade sebaceous carcinoma, and 1 squamous cell carcinoma...
December 2016: American Journal of Dermatopathology
https://www.readbyqxmd.com/read/27867722/feasibility-of-spatial-frequency-domain-imaging-sfdi-for-optically-characterizing-a-preclinical-oncology-model
#6
Syeda Tabassum, Yanyu Zhao, Raeef Istfan, Junjie Wu, David J Waxman, Darren Roblyer
Determination of chemotherapy efficacy early during treatment would provide more opportunities for physicians to alter and adapt treatment plans. Diffuse optical technologies may be ideally suited to track early biological events following chemotherapy administration due to low cost and high information content. We evaluated the use of spatial frequency domain imaging (SFDI) to characterize a small animal tumor model in order to move towards the goal of endogenous optical monitoring of cancer therapy in a controlled preclinical setting...
October 1, 2016: Biomedical Optics Express
https://www.readbyqxmd.com/read/27863562/molecular-imaging-and-precision-medicine-pet-computed-tomography-and-therapy-response-assessment-in-oncology
#7
REVIEW
Sara Sheikhbahaei, Esther Mena, Puskar Pattanayak, Mehdi Taghipour, Lilja B Solnes, Rathan M Subramaniam
A variety of methods have been developed to assess tumor response to therapy. Standardized qualitative criteria based on 18F-fluoro-deoxyglucose PET/computed tomography have been proposed to evaluate the treatment effectiveness in specific cancers and these allow more accurate therapy response assessment and survival prognostication. Multiple studies have addressed the utility of the volumetric PET biomarkers as prognostic indicators but there is no consensus about the preferred segmentation methodology for these metrics...
January 2017: PET Clinics
https://www.readbyqxmd.com/read/27863260/applications-of-dna-based-liquid-biopsy-for-central-nervous-system-neoplasms
#8
REVIEW
Joanna Wang, Chetan Bettegowda
The management of central nervous system malignancies remains reliant on histopathological analysis and neuroimaging, despite their complex genetic profile. The intratumoral heterogeneity displayed by these tumors necessitates a more sophisticated method of tumor analysis and monitoring, with the ability to assess tumors over space and time. Circulating biomarkers, including circulating tumor cells, circulating tumor DNA, and extracellular vesicles, hold promise as a type of real-time liquid biopsy able to provide dynamic information not only regarding tumor burden to monitor disease progression and treatment response, but also regarding genetic profile to enable changes in management to match a constantly evolving tumor...
November 15, 2016: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/27861749/the-challenges-of-tumor-genetic-diversity
#9
REVIEW
Edmund A Mroz, James W Rocco
The authors review and discuss the implications of genomic analyses documenting the diversity of tumors, both among patients and within individual tumors. Genetic diversity among solid tumors limits targeted therapies, because few mutations that drive tumors are both targetable and at high prevalence. Many more driver mutations and how they affect cellular signaling pathways must be identified if targeted therapy is to become widely useful. Genetic diversity within a tumor-intratumor genetic heterogeneity-makes the tumor a collection of subclones: related yet distinct cancers...
November 8, 2016: Cancer
https://www.readbyqxmd.com/read/27861510/heterogeneous-uptake-of-nanoparticles-in-mouse-models-of-pediatric-high-risk-neuroblastoma
#10
Ketan B Ghaghada, Zbigniew A Starosolski, Anna Lakoma, Caterina Kaffes, Saurabh Agarwal, Khannan K Athreya, Jason Shohet, Eugene Kim, Ananth Annapragada
Liposomal chemotherapeutics are exemplified by DOXIL® are commonly used in adult cancers. While these agents exhibit improved safety profile compared to their free drug counterparts, their treatment response rates have been ~ 20%, often attributed to the heterogeneous intratumoral uptake and distribution of liposomal nanoparticles. Non-invasive and quantitative monitoring of the uptake and distribution of liposomal nanoparticles in solid tumors could allow for patient stratification and personalized cancer nanomedicine...
2016: PloS One
https://www.readbyqxmd.com/read/27861143/intratumoral-heterogeneity-and-chemoresistance-in-nonseminomatous-germ-cell-tumor-of-the-testis
#11
Mehmet Asim Bilen, Kenneth R Hess, Matthew T Campbell, Jennifer Wang, Russell R Broaddus, Jose A Karam, John F Ward, Christopher G Wood, Seungtaek L Choi, Priya Rao, Miao Zhang, Aung Naing, Rosale General, Diana H Cauley, Sue-Hwa Lin, Christopher J Logothetis, Louis L Pisters, Shi-Ming Tu
BACKGROUND: Nonseminomatous germ cell tumor of the testis (NSGCT) is largely curable. However, a small group of patients develop refractory disease. We investigated the hypothesis that intratumoral heterogeneity contributes to the emergence of chemoresistance and the development of refractory tumor subtypes. RESULTS: Our institution's records for January 2000 through December 2010 included 275 patients whose primary tumor showed pure embryonal carcinoma (pure E); mixed embryonal carcinoma, yolk sac tumor, and teratoma (EYT); or mixed embryonal carcinoma, yolk sac tumor, seminoma, and teratoma (EYST)...
November 16, 2016: Oncotarget
https://www.readbyqxmd.com/read/27848916/tumoral-heterogeneity-of-breast-cancer
#12
Aurélie Roulot, Delphine Héquet, Jean-Marc Guinebretière, Anne Vincent-Salomon, Florence Lerebours, Coraline Dubot, Roman Rouzier
The objective of this literature review is to describe the types of tumor heterogeneity in breast cancer and their clinical implication. Two kinds of tumor heterogeneity are described: intertumor heterogeneity and intra-tumor heterogeneity. In breast cancer, inter-tumor heterogeneity was best characterized in the 2000s thanks to high throughput analyses. These analyzes resulted in a molecular classification of breast cancers distinguishing four subtypes: Luminal A, Luminal B, HER 2+ and basal like. This variability may be observed between the primary tumor and metastases, namely the temporal intratumor heterogeneity...
December 1, 2016: Annales de Biologie Clinique
https://www.readbyqxmd.com/read/27843810/braf-v600e-mutation-has-it-a-role-in-cervical-lymph-node-metastasis-of-papillary-thyroid-cancer
#13
Neslihan Kurtulmus, Burak Ertas, Yesim Saglican, Hakan Kaya, Umit Ince, Mete Duren
BACKGROUND: The BRAF(V600E) mutation is common in papillary thyroid cancer (PTC). Lymph node metastasis (LNM) may be associated with poor prognosis. However, the LNM mechanism remains unclear. OBJECTIVES: Our aim was to evaluate the prevalence of the BRAF(V600E) mutation in primary tumors and accompanying LNM at the time of diagnosis. METHODS: This retrospective study included 51 PTC patients (40 women, 11 men; mean age 40.0 ± 16.5 years; range 6-81) who underwent total thyroidectomy accompanied by a lateral neck dissection due to preoperatively detected LNM...
September 2016: European Thyroid Journal
https://www.readbyqxmd.com/read/27829147/adaptive-resistance-to-an-inhibitor-of-chromosomal-instability-in-human-cancer-cells
#14
Bernardo Orr, Lama Talje, Zhexian Liu, Benjamin H Kwok, Duane A Compton
Karyotype diversity is a hallmark of solid tumors that contributes to intratumor heterogeneity. This diversity is generated by persistent chromosome mis-segregation associated with chromosomal instability (CIN). CIN correlates with tumor relapse and is thought to promote drug resistance by creating a vast genomic landscape through which karyotypically unique clones survive lethal drug selection. We explore this proposition using a small molecule (UMK57) that suppresses chromosome mis-segregation in CIN cancer cells by potentiating the activity of the kinesin-13 protein MCAK...
November 8, 2016: Cell Reports
https://www.readbyqxmd.com/read/27822036/improvement-of-intratumor-microdistribution-of-pegylated-liposome-via-tumor-priming-by-metronomic-s-1-dosing
#15
Yusuke Doi, Amr S Abu Lila, Haruna Matsumoto, Tomoko Okada, Taro Shimizu, Tatsuhiro Ishida
The efficient delivery of nanocarrier-based cancer therapeutics into tumor tissue is problematic. Structural abnormalities, tumor vasculature heterogeneity, and elevated intratumor pressure impose barriers against the preferential accumulation of nanocarrier-based cancer therapeutics within tumor tissues and, consequently, compromise their therapeutic efficacy. Recently, we have reported that metronomic S-1, orally available tegafur formulation, dosing synergistically augmented the therapeutic efficacy of oxaliplatin (l-OHP)-containing PEGylated liposome without increasing the toxicity in animal model...
2016: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/27819858/18f-fdg-pet-ct-metabolic-tumor-volume-and-intratumoral-heterogeneity-in-pancreatic-adenocarcinomas-impact-of-dual-time-point-and-segmentation-methods
#16
Esther Mena, Sara Sheikhbahaei, Mehdi Taghipour, Abhinav K Jha, Esther Vicente, Jennifer Xiao, Rathan M Subramaniam
OBJECTIVES: We aimed to determine the consistency of quantitative PET measurements of metabolic tumor volume (MTV) and intratumoral heterogeneity index for primary untreated pancreatic adenocarcinomas, when using dual-time point F-FDG PET/CT imaging. METHODS: This is an institutional review board-approved, retrospective study including 71 patients with pancreatic adenocarcinoma, who underwent dual-time point F-FDG PET/CT imaging, at approximately 1 hour (early) and 2 hours (delayed), after injection...
November 4, 2016: Clinical Nuclear Medicine
https://www.readbyqxmd.com/read/27815126/programmed-cell-death-ligand-pd-l1-expression-in-stage-ii-and-iii-lung-adenocarcinomas-and-nodal-metastases
#17
Hironori Uruga, Emine Bozkurtlar, Tiffany G Huynh, Alona Muzikansky, Yasushi Goto, Maria Gomez-Caraballo, Aaron N Hata, Justin F Gainor, Eugene J Mark, Jeffrey A Engelman, Michael D Lanuti, Mari Mino-Kenudson
INTRODUCTION: PD-L1 expression by immunohistochemistry (IHC) may serve as a predictive biomarker for anti-PD-1/PD-L1 therapies; however, little is known about intertumoral heterogeneity of PD-L1 expression by IHC in lung adenocarcinomas (ADC), and there have been conflicting results on the prognostic role of PD-L1 expression in ADC. METHODS: PD-L1expression was evaluated in resected stage II and III ADC using various cutoffs, and was correlated with clinicopathologic parameters and survival...
November 1, 2016: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/27810697/lymphocyte-predominant-triple-negative-breast-carcinomas-in-premenopausal-patients-lower-expression-of-basal-immunohistochemical-markers
#18
Sergio Mitsuo Masili-Oku, Bernardo Gomes Lacerda de Almeida, Carlos Eduardo Bacchi, Jose Roberto Filassi, Edmund Chada Baracat, Filomena Marino Carvalho
OBJECTIVES: Triple-negative breast carcinomas (TNBCs) correspond to a molecular heterogeneous disease defined by lack of estrogen and progesterone receptor expression, and the absence of overexpression and/or amplification of HER2. Recent data indicate that clinical outcome in TNBC is affected by tumor-infiltrating lymphocytes, suggesting that they can benefit from immunotherapies. We selected 116 consecutive premenopausal patients with TNBC to compare the immunohistochemical profile of the group rich in tumor-infiltrating lymphocytes with those without this characteristic...
October 28, 2016: Breast: Official Journal of the European Society of Mastology
https://www.readbyqxmd.com/read/27807933/monochromatic-subdiffusive-spatial-frequency-domain-imaging-provides-in-situ-sensitivity-to-intratumoral-morphological-heterogeneity-in-a-murine-model
#19
David M McClatchy, P Jack Hoopes, Brian W Pogue, Stephen Chad Kanick
For the first time, spatially resolved quantitative metrics of light scattering recovered with sub-diffusive spatial frequency domain imaging (sd-SFDI) are shown to be sensitive to changes in intratumoral morphology and viability by direct comparison to histopathological analysis. Two freshly excised subcutaneous murine tumor cross-sections were measured with sd-SFDI, and recovered optical scatter parameter maps were co-registered to whole mount histology. Unique clustering of the optical scatter parameters μs' vs...
November 3, 2016: Journal of Biophotonics
https://www.readbyqxmd.com/read/27807831/quantitative-clinical-imaging-methods-for-monitoring-intratumoral-evolution
#20
Joo Yeun Kim, Robert A Gatenby
Solid tumors are multiscale, open, complex, dynamic systems: complex because they have many interacting components, dynamic because both the components and their interactions can change with time, and open because the tumor freely communicates with surrounding and even distant host tissue. Thus, it is not surprising that striking intratumoral variations are commonly observed in clinical imaging such as MRI and CT and that several recent studies found striking regional variations in the molecular properties of cancer cells from the same tumor...
2017: Methods in Molecular Biology
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