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https://www.readbyqxmd.com/read/28431273/chromosomal-instability-in-gastric-cancer-biology
#1
REVIEW
Saffiyeh Saboor Maleki, Christoph Röcken
Gastric cancer (GC) is the fifth most common cancer in the world and accounts for 7% of the total cancer incidence. The prognosis of GC is dismal in Western countries due to late diagnosis: approximately 70% of the patients die within 5 years following initial diagnosis. Recently, integrative genomic analyses led to the proposal of a molecular classification of GC into four subtypes, i.e.,microsatellite-instable, Epstein-Barr virus-positive, chromosomal-instable (CIN), and genomically stable GCs. Molecular classification of GC advances our knowledge of the biology of GC and may have implications for diagnostics and patient treatment...
April 18, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28429715/mapping-clinicopathological-entities-within-colorectal-mucinous-adenocarcinomas-a-hierarchical-clustering-approach
#2
Charly Liddell, Laure Droy-Dupré, Sylvie Métairie, Fabrice Airaud, Christelle Volteau, Stéphane Bezieau, Christian L Laboisse, Jean-François Mosnier
The aim of this study was to interrogate the heterogeneity of colorectal mucinous adenocarcinomas. This study is based on hierarchical clustering approach combining clinicopathological and molecular patterns known to be relevant to oncogenesis and therapeutic management of patients with colorectal carcinoma, ie, microsatellite instability, O6-methylguanine-DNA methyltransferase (MGMT) status, KRAS, and BRAF mutations and wnt signaling pathway activation. Comparison of the study group of 60 mucinous adenocarcinomas defined according to World Health Organization classification with control group of 136 colorectal adenocarcinomas successively removed shows higher frequency of BRAF and KRAS mutations and microsatellite instability-high status and lower frequency of wnt signaling pathway activation in mucinous adenocarcinomas...
April 21, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28426873/high-fat-diet-induced-leptin-and-wnt-expression-rna-sequencing-and-pathway-analysis-of-mouse-colonic-tissue-and-tumors
#3
Harrison M Penrose, Sandra Heller, Chloe Cable, Hani Nakhoul, Melody Baddoo, Erik Flemington, Susan E Crawford, Suzana D Savkovic
Obesity, an immense epidemic affecting approximately half a billion adults, has doubled in prevalence in the last several decades. Epidemiological data support that obesity, due to intake of a high-fat, western diet, increases the risk of colon cancer; however, the mechanisms underlying this risk remain unclear. Here, utilizing next generation RNA sequencing, we aimed to determine the high-fat diet (HFD) mediated expression profile in mouse colon and the azoxymethane/dextran sulfate sodium model of colon cancer...
March 1, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28423040/inheritance-patterns-of-atcct-repeat-interruptions-in-spinocerebellar-ataxia-type-10-sca10-expansions
#4
Ivette Landrian, Karen N McFarland, Jilin Liu, Connie J Mulligan, Astrid Rasmussen, Tetsuo Ashizawa
Spinocerebellar ataxia type 10 (SCA10), an autosomal dominant cerebellar ataxia disorder, is caused by a non-coding ATTCT microsatellite repeat expansion in the ataxin 10 gene. In a subset of SCA10 families, the 5'-end of the repeat expansion contains a complex sequence of penta- and heptanucleotide interruption motifs which is followed by a pure tract of tandem ATCCT repeats of unknown length at its 3'-end. Intriguingly, expansions that carry these interruption motifs correlate with an epileptic seizure phenotype and are unstable despite the theory that interruptions are expected to stabilize expanded repeats...
2017: PloS One
https://www.readbyqxmd.com/read/28422758/first-in-human-trial-of-multikinase-vegf-inhibitor-regorafenib-and-anti-egfr-antibody-cetuximab-in-advanced-cancer-patients
#5
Vivek Subbiah, Muhammad Rizwan Khawaja, David S Hong, Behrang Amini, Jiang Yungfang, Hui Liu, Adrienne Johnson, Alexa B Schrock, Siraj M Ali, James X Sun, David Fabrizio, Sarina Piha-Paul, Siqing Fu, Apostolia M Tsimberidou, Aung Naing, Filip Janku, Daniel D Karp, Michael Overman, Cathy Eng, Scott Kopetz, Funda Meric-Bernstam, Gerald S Falchook
BACKGROUND: The combination of multikinase VEGF inhibitor regorafenib and anti-EGFR antibody cetuximab overcomes intrinsic and acquired resistance in both EGFR-sensitive and EGFR-resistant preclinical models of colorectal cancer (CRC). METHODS: Utilizing a standard 3+3 design, a phase I study was designed to determine safety, maximum tolerated dose (MTD), and dose-limiting toxicities (DLTs) of the regorafenib plus cetuximab combination among patients with advanced cancer including CRC...
April 20, 2017: JCI Insight
https://www.readbyqxmd.com/read/28421339/small-bowel-adenocarcinoma-complicating-crohn-s-disease-a-single-centre-experience-emphasizing-the-importance-of-screening-for-dysplasia
#6
Chloé Grolleau, Nicolas M Pote, Nathalie S Guedj, Magaly Zappa, Nathalie Theou-Anton, Yoram Bouhnik, Yves Panis, Dominique L Cazals-Hatem
Small bowel adenocarcinoma (SBA) complicating Crohn's disease (CD) is rare and generally found incidentally on surgical specimens. We report our experience in CD-associated SBA observed this last decade in a tertiary referral centre in order to update its incidence, clinical presentation and pathological features. All SBAs diagnosed in patients who underwent surgery for CD between 2006 and 2016 were retrospectively included. Clinico-pathological characteristics were reviewed, and follow-up was updated. SBA was diagnosed in 9 (1...
April 18, 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/28420421/analysis-of-100-000-human-cancer-genomes-reveals-the-landscape-of-tumor-mutational-burden
#7
Zachary R Chalmers, Caitlin F Connelly, David Fabrizio, Laurie Gay, Siraj M Ali, Riley Ennis, Alexa Schrock, Brittany Campbell, Adam Shlien, Juliann Chmielecki, Franklin Huang, Yuting He, James Sun, Uri Tabori, Mark Kennedy, Daniel S Lieber, Steven Roels, Jared White, Geoffrey A Otto, Jeffrey S Ross, Levi Garraway, Vincent A Miller, Phillip J Stephens, Garrett M Frampton
BACKGROUND: High tumor mutational burden (TMB) is an emerging biomarker of sensitivity to immune checkpoint inhibitors and has been shown to be more significantly associated with response to PD-1 and PD-L1 blockade immunotherapy than PD-1 or PD-L1 expression, as measured by immunohistochemistry (IHC). The distribution of TMB and the subset of patients with high TMB has not been well characterized in the majority of cancer types. METHODS: In this study, we compare TMB measured by a targeted comprehensive genomic profiling (CGP) assay to TMB measured by exome sequencing and simulate the expected variance in TMB when sequencing less than the whole exome...
April 19, 2017: Genome Medicine
https://www.readbyqxmd.com/read/28418918/the-pd-1-pd-l1-expression-and-cd3-t-cell-infiltration-in-relation-to-outcome-in-advanced-gastric-signet-ring-cell-carcinoma-representing-a-potential-biomarker-for-immunotherapy
#8
Shenying Jin, Bo Xu, Lixia Yu, Yao Fu, Hongyan Wu, Xiangshan Fan, Jia Wei, Baorui Liu
Recent data supports a potentially significant role for immune checkpoint inhibitors in the treatment of gastric cancer. However, there are few data on the clinical implications of immunotherapy markers in gastric signet-ring cell carcinoma (SRCC). We evaluated the expression of programmed cell death protein-1 (PD-1), programmed cell death ligand 1(PD-L1), infiltration by CD3+ T cell, microsatellite instability (MSI), and Epstein-Barr Virus (EBV), and the relationship of each factor to survival in 89 advanced SRCC patients...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28416736/nomo-1-gene-is-deleted-in-early-onset-colorectal-cancer
#9
José Perea, Juan Luis García, Jessica Pérez, Daniel Rueda, María Arriba, Yolanda Rodríguez, Miguel Urioste, Rogelio González-Sarmiento
To characterize clinical features of a recurrent alteration in 16p13.12-p13.11 in Colorectal Cancer (CRC), mainly in Early-onset subgroup (EOCRC), and to assess the status of NOMO1, a gene located in that region, we analyzed differential clinicopathological, familial and molecular features of CRC subsets with and without alterations in the 16p13.12-p13.11, in global and EOCRC groups. We confirmed the region by fluorescence in-situ hybridization, and Quantitative Real-Time PCR analyzed the status of NOMO1 in different age-of-onset and Microsatellite Instability (MSI)-status CRC subsets...
February 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28416640/microsatellite-analysis-of-sporadic-and-hereditary-gynaecological-cancer-in-routine-diagnostics
#10
Laura Libera, Nora Sahnane, Ileana Wanda Carnevali, Laura Cimetti, Roberta Cerutti, Anna Maria Chiaravalli, Cristina Riva, Maria Grazia Tibiletti, Fausto Sessa, Daniela Furlan
Microsatellite instability (MSI) testing is tricky in gynaecological cancers (GC). Thus, we aimed to describe the instability patterns to improve MSI test interpretation in sporadic and hereditary GCs. Ninety-five cases, including uterine and ovarian cancers, with known genetic and immunohistochemical (IHC) features, were analysed for MSI by a mononucleotide repeats pentaplex (MRP). We identified 13 ambiguous cases that did not fully meet MSI criteria ('borderline' cases, B-MSI), which were mainly represented by MSH2/MSH6-deficient and Lynch syndrome cases...
April 17, 2017: Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28412781/molecular-testing-to-optimize-and-personalize-decision-making-in-the-management-of-colorectal-cancer
#11
REVIEW
Marwan Al-Hajeili, Anthony F Shields, Jimmy J Hwang, Raymond C Wadlow, John L Marshall
Recent improvements in our understanding of the biology of colorectal cancer have led to the identification of several important prognostic and predictive markers of disease-associated risk and treatment response for the individual patient. Proper utilization of these biomarkers can enable physicians to tailor therapeutic strategies to maximize the likelihood of response and minimize treatment toxicity. In the management of colorectal cancer, tremendous progress has been made in the development of strategies for immune checkpoint inhibition; in refinement of agents and approaches used in targeted therapy; and in techniques for molecular subtyping of tumor samples that have identified patient subgroups with clinically relevant cellular differences potentially affecting clinical management and treatment outcome...
April 15, 2017: Oncology (Williston Park, NY)
https://www.readbyqxmd.com/read/28412752/clinicopathologic-implications-of-immune-classification-by-pd-l1-expression-and-cd8-positive-tumor-infiltrating-lymphocytes-in-stage-ii-and-iii-gastric-cancer-patients
#12
Jiwon Koh, Chan-Young Ock, Jin Won Kim, Soo Kyung Nam, Yoonjin Kwak, Sumi Yun, Sang-Hoon Ahn, Do Joong Park, Hyung-Ho Kim, Woo Ho Kim, Hye Seung Lee
We co-assessed PD-L1 expression and CD8+ tumor-infiltrating lymphocytes in gastric cancer (GC), and categorized into 4 microenvironment immune types. Immunohistochemistry (PD-L1, CD8, Foxp3, E-cadherin, and p53), PD-L1 mRNA in situ hybridization (ISH), microsatellite instability (MSI), and EBV ISH were performed in 392 stage II/III GCs treated with curative surgery and fluoropyrimidine-based adjuvant chemotherapy, and two public genome databases were analyzed for validation. PD-L1+ was found in 98/392 GCs (25...
February 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28409725/genetic-landscape-of-sporadic-vestibular-schwannoma
#13
Aril Løge Håvik, Ove Bruland, Erling Myrseth, Hrvoje Miletic, Mads Aarhus, Per-Morten Knappskog, Morten Lund-Johansen
OBJECTIVE Vestibular schwannoma (VS) is a benign tumor with associated morbidities and reduced quality of life. Except for mutations in NF2, the genetic landscape of VS remains to be elucidated. Little is known about the effect of Gamma Knife radiosurgery (GKRS) on the VS genome. The aim of this study was to characterize mutations occurring in this tumor to identify new genes and signaling pathways important for the development of VS. In addition, the authors sought to evaluate whether GKRS resulted in an increase in the number of mutations...
April 14, 2017: Journal of Neurosurgery
https://www.readbyqxmd.com/read/28408840/clinical-course-and-outcome-of-patients-with-high-level-microsatellite-instability-cancers-in-a-real-life-setting-a-retrospective-analysis
#14
Naama Halpern, Yael Goldberg, Luna Kadouri, Morasha Duvdevani, Tamar Hamburger, Tamar Peretz, Ayala Hubert
BACKGROUND: The prognostic and predictive significance of the high-level microsatellite instability (MSI-H) phenotype in various malignancies is unclear. We describe the characteristics, clinical course, and outcomes of patients with MSI-H malignancies treated in a real-life hospital setting. PATIENTS AND METHODS: A retrospective analysis of MSI-H cancer patient files was conducted. We analyzed the genetic data, clinical characteristics, and oncological treatments, including chemotherapy and surgical interventions...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28408773/can-mitochondria-dna-provide-a-novel-biomarker-for-evaluating-the-risk-and-prognosis-of-colorectal-cancer
#15
REVIEW
Han Shuwen, Yang Xi, Pan Yuefen
Colorectal cancer (CRC) was one of the most frequent cancers worldwide. Accurate risk and prognosis evaluation could obtain better quality of life and longer survival time for the patients. Current research hotspot was focus on the gene biomarker to evaluate the risk and prognosis. Mitochondrion contains its own DNA and regulates self-replicating so that it can be as a candidate biomarker for evaluating the risk and prognosis of colorectal cancer. But there were already huge controversies on this issue. The review was to summarize current viewpoints of the controversial issues and described our understanding from the four aspects including mtDNA copy number, mitochondrial displacement loop, mtDNA variation, and mtDNA microsatellite instability, wishing the summary of the mtDNA in colorectal cancer could provide a meaningful reference or a valuable direction in the future studies...
2017: Disease Markers
https://www.readbyqxmd.com/read/28406723/aspirin-use-and-colorectal-cancer-survival-according-to-tumor-cd274-programmed-cell-death-1-ligand-1-expression-status
#16
Tsuyoshi Hamada, Yin Cao, Zhi Rong Qian, Yohei Masugi, Jonathan A Nowak, Juhong Yang, Mingyang Song, Kosuke Mima, Keisuke Kosumi, Li Liu, Yan Shi, Annacarolina da Silva, Mancang Gu, Wanwan Li, NaNa Keum, Xuehong Zhang, Kana Wu, Jeffrey A Meyerhardt, Edward L Giovannucci, Marios Giannakis, Scott J Rodig, Gordon J Freeman, Daniel Nevo, Molin Wang, Andrew T Chan, Charles S Fuchs, Reiko Nishihara, Shuji Ogino
Purpose Blockade of the programmed cell death 1 (PDCD1, PD-1) immune checkpoint pathway can improve clinical outcomes in various malignancies. Evidence suggests that aspirin (a widely used nonsteroidal anti-inflammatory drug) not only prolongs colorectal cancer survival, but can also activate T cell-mediated antitumor immunity and synergize with immunotherapy through inhibition of prostaglandin E2 production. We hypothesized that the survival benefit associated with aspirin might be stronger in colorectal carcinoma with a lower CD274 (PDCD1 ligand 1, PD-L1) expression level that resulted in lower signaling of the immune checkpoint pathway...
April 13, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28405764/prognostic-implication-of-cd274-pd-l1-protein-expression-in-tumor-infiltrating-immune-cells-for-microsatellite-unstable-and-stable-colorectal-cancer
#17
Kyu Sang Lee, Yoonjin Kwak, Soyeon Ahn, Eun Shin, Heung-Kwon Oh, Duck-Woo Kim, Sung-Bum Kang, Gheeyoung Choe, Woo Ho Kim, Hye Seung Lee
In this study, we investigated the clinical relevance of CD274 (PD-L1) protein expression by tumor cells and tumor-infiltrating immune cells in colorectal cancer (CRC). To this end, 186 microsatellite instability-high (MSI-H) and 153 microsatellite stable (MSS) CRCs were subjected to immunohistochemistry (IHC) analysis for the expression of CD274 and mismatch repair proteins. CD274 expression was evaluated in tumor cells at the center (TC) and periphery (TP), and immune cells at the center (IC) and periphery (IP) of CRC...
April 12, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28405513/tumor-sqstm1-p62-expression-and-t-cells-in-colorectal-cancer
#18
Keisuke Kosumi, Yohei Masugi, Juhong Yang, Zhi Rong Qian, Sun A Kim, Wanwan Li, Yan Shi, Annacarolina da Silva, Tsuyoshi Hamada, Li Liu, Mancang Gu, Tyler S Twombly, Yin Cao, David A Barbie, Katsuhiko Nosho, Hideo Baba, Wendy S Garrett, Jeffery A Meyerhardt, Edward L Giovannucci, Andrew T Chan, Charles S Fuchs, Shuji Ogino, Reiko Nishihara
Evidence suggests that activation of autophagy in neoplastic cells potentiates antitumor immunity through cross-presentation of tumor-associated antigens to T cells and release of immune mediators. The SQSTM1 (sequestosome 1, p62) protein is degraded by activated autophagy, and might enhance immune response to tumor cells. We hypothesized that tumor SQSTM1 expression level might be inversely associated with T-cell densities in colorectal carcinoma tissue. We evaluated tumor SQSTM1 expression by immunohistochemistry in 601 rectal and colon cancer cases within the Nurses' Health Study and Health Professionals Follow-up Study...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28405512/high-expression-of-pd-1-ligands-is-associated-with-kataegis-mutational-signature-and-apobec3-alterations
#19
Amélie Boichard, Igor F Tsigelny, Razelle Kurzrock
Immunotherapy with checkpoint inhibitors, such as antibodies blocking the programmed cell-death receptor-1 (PD-1), has resulted in remarkable responses in patients having traditionally refractory cancers. Although response to PD-1 inhibitors correlates with PD-1 ligand (PD-L1 or PD-L2) expression, PD-1 ligand positivity represents only a part of the predictive model necessary for selecting patients predisposed to respond to immunotherapy. We used all genomic, transcriptomic, proteomic and phenotypic data related to 8,475 pan-cancer samples available in The Cancer Genome Atlas (TCGA) and conducted a logistic regression analysis based on a large set of variables, such as microsatellite instability (MSI-H), mismatch repair (MMR) alterations, polymerase δ (POLD1) and polymerase ε (POLE) mutations, activation-induced/apolipoprotein-B editing cytidine deaminases (AID/APOBEC) alterations, lymphocyte markers and mutation burden estimates to determine independent factors that associate with PD-1 ligand overexpression...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28401534/competing-risks-analysis-of-microsatellite-instability-as-a-prognostic-factor-in-colorectal-cancer
#20
J Toh, P H Chapuis, L Bokey, C Chan, K J Spring, O F Dent
BACKGROUND: Despite an extensive literature suggesting that high microsatellite instability (MSI-H) enhances survival and protects against recurrence after colorectal cancer resection, such effects remain controversial as many studies show only a weak bivariate association or no multivariable association with outcome. This study examined the relationship between MSI status and colorectal cancer outcomes with adjustment for death from other causes as a competing risk. METHODS: A hospital database of patients following colorectal cancer resection was interrogated for clinical, operative, pathology, adjuvant therapy and follow-up information...
April 12, 2017: British Journal of Surgery
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