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Microsatellite instability

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https://www.readbyqxmd.com/read/28533942/hla-a24-ligandome-analysis-of-colon-and-lung-cancer-cells-identifies-a-novel-cancer-testis-antigen-and-a-neoantigen-that-elicits-specific-and-strong-ctl-responses
#1
Vitaly Kochin, Takayuki Kanaseki, Serina Tokita, Sho Miyamoto, Yosuke Shionoya, Yasuhiro Kikuchi, Daichi Morooka, Yoshihiko Hirohashi, Tomohide Tsukahara, Kazue Watanabe, Shingo Toji, Yasuo Kokai, Noriyuki Sato, Toshihiko Torigoe
This study focused on HLA-A24 and comprehensively analyzed the ligandome of colon and lung cancer cells without the use of MHC-binding in silico prediction algorithms. Affinity purification using the antibody specific to HLA-A24 followed by LC-MS/MS sequencing was used to detect peptides, which harbored the known characteristics of HLA-A24 peptides in terms of length and anchor motifs. Ligandome analysis demonstrated the natural presentation of two different types of novel tumor-associated antigens. The ligandome contained a peptide derived from SUV39H2, a gene found to be expressed in a variety of cancers but not in normal tissues (except for the testis)...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28533824/analysis-of-the-dna-methylation-level-of-cancer-related-genes-in-colorectal-cancer-and-the-surrounding-normal-mucosa
#2
Tamotsu Sugai, Masakazu Yoshida, Makoto Eizuka, Noriyuki Uesugii, Wataru Habano, Kouki Otsuka, Akira Sasaki, Eiichiro Yamamoto, Takayuki Matsumoto, Hiromu Suzuki
BACKGROUND: Two molecular pathways promote the development of colorectal cancer (CRC). One is termed "microsatellite stable" (MSS) whereas the other is characterized by "microsatellite instability" (MSI or MIN). In addition, the CpG island methylation phenotype is known to be an important alteration as a third molecular type. Thus, DNA methylation is thought to provide potential biomarkers for assessment of cancer risk in normal mucosa. In addition, it is also known that colonic location is an important parameter in the development of CRC...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28533658/checkpoint-inhibitors-in-gastrointestinal-cancers-expectations-and-reality
#3
EDITORIAL
Hampig Raphael Kourie, Samer Tabchi, Marwan Ghosn
Immune checkpoint inhibitors represent revolutionary anti-cancer agents, being rapidly approved in different malignancies and settings. Gastrointestinal (GI) cancers represent a wide variety of tumors with specific characteristics and different responses to various therapeutic alternatives; while some are chemo-sensitive others are chemo-resistant and only respond to more aggressive cytotoxic regimens, targeted therapies or a combination of both. Preliminary results of immune checkpoint inhibitors in some GI cancers are promising, namely in hepatocellular carcinoma, anal cancers and microsatellite instability high colorectal cancers...
May 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28531315/the-interaction-between-cytosine-methylation-and-processes-of-dna-replication-and-repair-shape-the-mutational-landscape-of-cancer-genomes
#4
Rebecca C Poulos, Jake Olivier, Jason W H Wong
Methylated cytosines (5mCs) are frequently mutated in the genome. However, no studies have yet comprehensively analysed mutation-methylation associations across cancer types. Here we analyse 916 cancer genomes, together with tissue type-specific methylation and replication timing data. We describe a strong mutation-methylation association across colorectal cancer subtypes, most interestingly in samples with microsatellite instability (MSI) or Polymerase epsilon (POLE) exonuclease domain mutations. By analysing genomic regions with differential mismatch repair (MMR) efficiency, we suggest a possible role for MMR in the correction of 5mC deamination events, potentially accounting for the high rate of 5mC mutation accumulation in MSI tumours...
May 22, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28529742/intraductal-tubulopapillary-neoplasm-accompanied-by-invasive-carcinoma-of-the-pancreas-a-case-report-and-review-of-the-literature
#5
Li Niu, Zhigao Xu, Huan Liu, Hong Cao, Guifang Yang
Intraductal tubulopapillary neoplasms (ITPNs) are rare pancreatic neoplasms accounting for ~0.4% of pancreatic tumors. However, their clinicopathological characteristics have not been clearly determined and the number of available clinical studies on this type of tumor is limited at present. Due to the rare incidence of ITPN, diagnosis is often delayed. We herein present a unique case of a 38-year-old man who was diagnosed with ITPN accompanied with invasive carcinoma of the pancreas and underwent total pancreatectomy...
May 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28528517/loss-of-msh2-and-msh6-due-to-heterozygous-germline-defects-in-msh3-and-msh6
#6
Monika Morak, Sarah Käsbauer, Martina Kerscher, Andreas Laner, Anke M Nissen, Anna Benet-Pagès, Hans K Schackert, Gisela Keller, Trisari Massdorf, Elke Holinski-Feder
Lynch Syndrome (LS) is the most common dominantly inherited colorectal cancer (CRC) predisposition and is caused by a heterozygous germline defect in one of the DNA mismatch repair (MMR) genes MLH1, MSH2, MSH6, or PMS2. High microsatellite instability (MSI-H) and loss of MMR protein expression in tumours reflecting a defective MMR are indicators for LS, as well as a positive family history of early onset CRC. MSH2 and MSH6 form a major functional heterodimer, and MSH3 is an alternative binding partner for MSH2...
May 20, 2017: Familial Cancer
https://www.readbyqxmd.com/read/28525661/comparison-between-mononucleotide-and-dinucleotide-marker-panels-in-gastric-cancer-with-loss-of-hmlh1-or-hmsh2-expression
#7
Jeong Goo Kim, Soyoung Shin, Joonhong Park
BACKGROUND: DNA mismatch repair deficiency is an important molecular mechanism of genetic instability in gastric cancer, and a high instability at microsatellites is associated with favorable prognosis. We compared mononucleotide and dinucleotide microsatellite instability (MSI) marker panels in 56 paired gastric tumor and normal samples. METHODS: The mononucleotide marker panel (mono panel) consisted of 8 markers: BAT25, BAT26, BAT40, BAT-RII, NR21, NR22, NR24 and NR27...
May 16, 2017: International Journal of Biological Markers
https://www.readbyqxmd.com/read/28522602/can-microsatellite-status-of-colorectal-cancer-be-reliably-assessed-after-neoadjuvant-therapy
#8
Jennifer B Goldstein, William Wu, Ester Borras, Gita Masand, Amanda Cuddy, Maureen E Mork, Sarah Bannon, Patrick M Lynch, Miguel Rodriguez-Bigas, Melissa Taggart, Ji Wu, Paul Scheet, Scott Kopetz, Y Nancy You, Eduardo Vilar
Purpose: Determination of microsatellite instability (MSI) by PCR is the gold standard; however, immunohistochemistry (IHC) of mismatch repair (MMR) proteins is frequently performed instead. The reliability of these methods on post-neoadjuvant-therapy specimens is unknown.  We examined the effect of neoadjuvant therapy on MSI results by PCR and IHC. Experimental design: A total of 239 colorectal cancers resected after neoadjuvant therapy were assessed for MSI with PCR and IHC. PCR and IHC results for matched paired pre- and post-treatment specimens were compared...
May 18, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28515943/evaluation-of-dosing-strategy-for-pembrolizumab-for-oncology-indications
#9
Tomoko Freshwater, Anna Kondic, Malidi Ahamadi, Claire H Li, Rik de Greef, Dinesh de Alwis, Julie A Stone
BACKGROUND: Traditionally, most monoclonal antibodies (mAbs) have been dosed based on body weight because of perceived contribution of body size in pharmacokinetic variability. The same approach was used in the initial pembrolizumab studies; however, following availability of PK data, the need for weight-based dosing for pembrolizumab was reassessed. METHODS: A previously established population PK (popPK) model as well as exposure-response results from patients with advanced melanoma or non-small cell lung cancer (NSCLC) were used to evaluate the potential application of a fixed dosing regimen with the aim of maintaining pembrolizumab exposures within the range demonstrated to provide near maximal efficacy and acceptable safety...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28512763/impact-of-mlh1-expression-on-tumour-evolution-after-curative-surgical-tumour-resection-in-a-murine-orthotopic-xenograft-model-for-human-msi-colon-cancer
#10
Katy Meunier, Marianne Ferron, Claire Calmel, Jean-François Fléjou, Marc Pocard, Françoise Praz
Colorectal cancers (CRCs) displaying microsatellite instability (MSI) most often result from MLH1 deficiency. The aim of this study was to assess the impact of MLH1 expression per se on tumour evolution after curative surgical resection using a xenograft tumour model. Transplantable tumours established with the human MLH1-deficient HCT116 cell line and its MLH1-complemented isogenic clone, mlh1-3, were implanted onto the caecum of NOD/SCID mice. Curative surgical resection was performed at day 10 in half of the animals...
May 16, 2017: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/28510098/body-mass-index-and-risk-of-colorectal-carcinoma-subtypes-classified-by-tumor-differentiation-status
#11
Akiko Hanyuda, Yin Cao, Tsuyoshi Hamada, Jonathan A Nowak, Zhi Rong Qian, Yohei Masugi, Annacarolina da Silva, Li Liu, Keisuke Kosumi, Thing Rinda Soong, Iny Jhun, Kana Wu, Xuehong Zhang, Mingyang Song, Jeffrey A Meyerhardt, Andrew T Chan, Charles S Fuchs, Edward L Giovannucci, Shuji Ogino, Reiko Nishihara
Previous studies suggest that abnormal energy balance status may dysregulate intestinal epithelial homeostasis and promote colorectal carcinogenesis, yet little is known about how host energy balance and obesity influence enterocyte differentiation during carcinogenesis. We hypothesized that the association between high body mass index (BMI) and colorectal carcinoma incidence might differ according to tumor histopathologic differentiation status. Using databases of the Nurses' Health Study and Health Professionals Follow-up Study, and duplication-method Cox proportional hazards models, we prospectively examined an association between BMI and the incidence of colorectal carcinoma subtypes classified by differentiation features...
May 16, 2017: European Journal of Epidemiology
https://www.readbyqxmd.com/read/28510097/ago-austria-recommendation-on-screening-and-diagnosis-of-lynch-syndrome-ls
#12
Alain G Zeimet, Harald Mori, Edgar Petru, Stephan Polterauer, Alexander Reinthaller, Christian Schauer, Tonja Scholl-Firon, Christian Singer, Katharina Wimmer, Johannes Zschocke, Christian Marth
PURPOSE: This manuscript reports the consensus recommendations on screening and diagnosis of Lynch syndrome (LS) in patients with endometrial or ovarian cancer as well as on possible preventive measures in effectively LS-diagnosed women. The recommendations are issued by the Austrian Arbeitsgemeinschaft für Gynäkologische Onkologie (AGO) of the Österreichischen Gesellschaft für Gynäkologie und Geburtshilfe (OEGGG) after consultation of the most recent and relevant literature and following deliberation by the Genetic Task-Force convoked May, 2015 by the AGO Council...
May 16, 2017: Archives of Gynecology and Obstetrics
https://www.readbyqxmd.com/read/28509323/triple-negative-endometrial-cancer
#13
Michał Bulsa, Elżbieta Urasińska
Endometrial cancer (EC) is the most common malignancy of the female genital tract in the developed countries. In Poland, EC incidence increased from 3.496 to 5.251 between 2000 and 2011, with 5.251 new cases were diagnosed in 2011 alone, and this upward trend is expected to continue. There are two types of endometrial cancer: estrogen- related type I (approximately 80% of the cases) and unrelated to estrogen type II. Type I includes adenocarcinomas which grow slowly, have better prognosis, superficially infiltrate the myometrium, originate from endometrial hyperplasia without atypia, and occur before and after menopause...
2017: Ginekologia Polska
https://www.readbyqxmd.com/read/28507809/t-cell-therapy-targeting-a-public-neoantigen-in-microsatellite-instable-colon-cancer-reduces-in-vivo-tumor-growth
#14
Else M Inderberg, Sébastien Wälchli, Marit R Myhre, Sissel Trachsel, Hilde Almåsbak, Gunnar Kvalheim, Gustav Gaudernack
T-cell receptor (TCR) transfer is an attractive strategy to increase the number of cancer-specific T cells in adoptive cell therapy. However, recent clinical and pre-clinical findings indicate that careful consideration of the target antigen is required to limit the risk of off-target toxicity. Directing T cells against mutated proteins such as frequently occurring frameshift mutations may thus be a safer alternative to tumor-associated self-antigens. Furthermore, such frameshift mutations result in novel polypeptides allowing selection of TCRs from the non-tolerant T-cell repertoire circumventing the problem of low affinity TCRs due to central tolerance...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28507641/a-case-report-of-muir-torre-syndrome-in-a-woman-with-breast-cancer-and-msi-low-skin-squamous-cell-carcinoma
#15
Caroline Kientz, Marie-Odile Joly, Laurence Faivre, Alix Clemenson, Sophie Dalac, Côme Lepage, Caroline Chapusot, Caroline Jacquot, Renaud Schiappa, Marine Lebrun
BACKGROUND: The tumor spectrum in the Lynch syndrome is well defined, comprising an increased risk of developing colonic and extracolonic malignancies. Muir-Torre syndrome is a variant with a higher risk of skin disease. Patients have been described carrying mutations in the mismatch repair genes and presenting tumors with unusual histology or affected organ not part of the Lynch syndrome spectrum. Hence, the real link between Lynch syndrome, or Muir-Torre syndrome, and these tumors remains difficult to assess...
2017: Hereditary Cancer in Clinical Practice
https://www.readbyqxmd.com/read/28507204/detection-of-an-alk-fusion-in-colorectal-carcinoma-by-hybrid-capture-based-assay-of-circulating-tumor-dna
#16
Andrea Z Lai, Alexa B Schrock, Rachel L Erlich, Jeffrey S Ross, Vincent A Miller, Evgeny Yakirevich, Siraj M Ali, Fadi Braiteh
ALK rearrangements have been observed in 0.05%-2.5% of patients with colorectal cancers (CRCs) and are predicted to be oncogenic drivers largely mutually exclusive of KRAS, NRAS, or BRAF alterations. Here we present the case of a patient with metastatic CRC who was treatment naïve at the time of molecular testing. Initial ALK immunohistochemistry (IHC) staining was negative, but parallel genomic profiling of both circulating tumor DNA (ctDNA) and tissue using similar hybrid capture-based assays each identified an identical STRN-ALK fusion...
May 15, 2017: Oncologist
https://www.readbyqxmd.com/read/28498244/identifying-lynch-syndrome-in-women-presenting-with-endometrial-carcinoma-under-the-age-of-50-years
#17
Antonios Anagnostopoulos, Vicky H McKay, Iris Cooper, Fiona Campbell, Lynn Greenhalgh, John Kirwan
BACKGROUND: Lynch syndrome (LS) is an inherited disorder associated with genetic predisposition to endometrial, colorectal, ovarian, and other cancers. There is consensus for the necessity of assessment for LS in view of the established survival benefits for identified patients and affected family members. The debate regarding the best screening policy is far from being concluded. OBJECTIVES: The aim of this study was to evaluate a realistic protocol for identifying LS families by assessing young women with a diagnosis of endometrial cancer (EC)...
June 2017: International Journal of Gynecological Cancer
https://www.readbyqxmd.com/read/28485815/somatic-mutation-profiles-of-clear-cell-endometrial-tumors-revealed-by-whole-exome-and-targeted-gene-sequencing
#18
Matthieu Le Gallo, Meghan L Rudd, Mary Ellen Urick, Nancy F Hansen, Suiyuan Zhang, Fred Lozy, Dennis C Sgroi, August Vidal Bel, Xavier Matias-Guiu, Russell R Broaddus, Karen H Lu, Douglas A Levine, David G Mutch, Paul J Goodfellow, Helga B Salvesen, James C Mullikin, Daphne W Bell
BACKGROUND: The molecular pathogenesis of clear cell endometrial cancer (CCEC), a tumor type with a relatively unfavorable prognosis, is not well defined. We searched exome-wide for novel somatically mutated genes in CCEC and assessed the mutational spectrum of known and candidate driver genes in a large cohort of cases. METHODS: We conducted whole exome sequencing of paired tumor-normal DNAs from 16 cases of CCEC (12 CCECs and the CCEC components of 4 mixed histology tumors)...
May 9, 2017: Cancer
https://www.readbyqxmd.com/read/28485341/microsatellite-instability-in-stage-ii-colorectal-cancer-an-indian-perspective
#19
A P Dubey, S Vishwanath, P Nikhil, A Rathore, A Pathak
INTRODUCTION: Around 80% of colorectal carcinoma are associated with chromosomal instability (CIN) while rest of 20 % are euploid, possessing defect in mis match repair system (MMR) quintessential for surveillance and correction of errors in introduced into microsatellites. MATERIALS AND METHODS: We analyse all stage II CRC for MSI who presented at MDTC at Army hospital (research and refrral) new delhi during last 2 years (Jan 14 to Dec 2015). RESULTS: We found that 22...
October 2016: Indian Journal of Cancer
https://www.readbyqxmd.com/read/28471861/somatic-testing-on-gynecological-cancers-improve-the-identification-of-lynch-syndrome
#20
Ileana Carnevali, Laura Libera, Annamaria Chiaravalli, Nora Sahnane, Daniela Furlan, Alessandra Viel, Giulia Cini, Laura Cimetti, Thomas Rossi, Giorgio Formenti, Fabio Ghezzi, Cristina Riva, Fausto Sessa, Maria Grazia Tibiletti
OBJECTIVE: Recent data from the literature indicate gynecological cancers (GCs) as sentinel cancers for a diagnosis of Lynch syndrome (LS). Clinical approaches to identifying LS have low sensitivity, whereas somatic tests on GCs may be a more sensitive and cost-effective strategy. METHODS: A series of 78 GCs belonging to 74 patients sent to the Genetic Counselling Service were investigated using microsatellite instability, immunohistochemical expression of mismatch repair (MMR) genes, and MLH1 promoter methylation...
May 2, 2017: International Journal of Gynecological Cancer
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