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kras mutation in rectum cancer

Binnur Bagci, Musa Sari, Kursat Karadayi, Mustafa Turan, Ozturk Ozdemir, Gokhan Bagci
BACKGROUND: Colorectal cancer is a serious disease that causes significant morbidity and mortality in developed countries. Genetic changes, such as mutations in proto-oncogenes and DNA repair genes, and loss of function in the tumor suppressor genes cause colorectal cancer development. Abnormal DNA methylation is also known to play a crucial role in colorectal carcinogenesis. OBJECTIVE: In this study, frequencies of KRAS and BRAF mutations, promoter hypermethylation profiles of SFRP2, DAPK1, MGMT, HIC1 and p16 genes, and possible associations between hypermethylation of these genes and KRAS and BRAF mutations were aimed to find out...
June 24, 2016: Cancer Biomarkers: Section A of Disease Markers
Roberta Grande, Clara Natoli, Fabrizio Ciancola, Donatello Gemma, Arianna Pellegrino, Ida Pavese, Carlo Garufi, Luigi Di Lauro, Domenico Corsi, Diego Signorelli, Isabella Sperduti, Giada Cortese, Emanuela Risi, Federica Morano, Domenico Sergi, Carlo Signorelli, Enzo Maria Ruggeri, Germano Zampa, Marco Russano, Teresa Gamucci
BACKGROUND: Colorectal cancer patients have a median age of incidence >65years although they are largely under-represented in phase-III trials. This large population contains patients unfit for treatment, those suitable for monotherapy or for doublets and the impact of chemotherapy outside clinical trial is unclear. The aim of the study was to retrospectively analyse Overall Survival(OS) of elderly metastatic colorectal cancer(mCRC) patients treated with chemotherapy in daily practice...
2016: PloS One
Patrícia Silva, Cristina Albuquerque, Pedro Lage, Vanessa Fontes, Ricardo Fonseca, Inês Vitoriano, Bruno Filipe, Paula Rodrigues, Susana Moita, Sara Ferreira, Rita Sousa, Isabel Claro, Carlos Nobre Leitão, Paula Chaves, António Dias Pereira
Serrated polyposis (SPP) is characterized by the development of multiple serrated polyps and an increased predisposition to colorectal cancer (CRC). In the present study, we aimed to characterize, at a clinical and molecular level, a cohort of SPP patients with or without a family history of SPP and/or polyps/CRC (SPP-FHP/CRC). Sixty-two lesions from 12 patients with SPP-FHP/CRC and 6 patients with sporadic SPP were included. The patients with SPP-FHP/CRC presented with an older mean age at diagnosis (p=0...
September 2016: International Journal of Molecular Medicine
Kazunari Sasaki, Georgios A Margonis, Ana Wilson, Yuhree Kim, Stefan Buettner, Nikolaos Andreatos, Faiz Gani, Neda Amini, Gaya Spolverato, Timothy M Pawlik
BACKGROUND: Right-sided and left-sided colorectal cancer (CRC) is known to differ in their molecular carcinogenic pathways. We sought to investigate the variable prognostic implication of KRAS mutation after hepatectomy for colorectal liver metastases (CRLM) according to the site of primary CRC. METHODS: A total of 426 patients who underwent a curative-intent hepatic resection and whose KRAS status was available were identified. Clinicopathologic characteristics and long-term outcomes were stratified by KRAS status (wild type vs...
October 2016: Annals of Surgical Oncology
Muhammad Asif, Armaghan Shafaei, Seyedeh Fatemeh Jafari, Shazmin Kithur Mohamed, Mohammed Oday Ezzat, Aman Shah Abdul Majid, Chern Ein Oon, Sven H Petersen, Koji Kono, Amin Malik Shah Abdul Majid
Colorectal cancer (CRC) is one of the most common human malignant tumors worldwide. Arising from the transformation of epithelial cells in the colon and/or rectum into malignant cells, the foundation of CRC pathogenesis lies in the progressive accumulation of mutations in oncogenes and tumor-suppressor genes, such as KRAS and APC. Resistance to apoptosis is one of the key mechanisms in the development of CRC as it is for any other kind of cancer. Natural products have been shown to induce the expression of apoptosis regulators that are blocked in cancer cells...
August 22, 2016: Toxicology Letters
Djeda Belharazem, Julia Magdeburg, Ann-Kristin Berton, Li Beissbarth, Christian Sauer, Carsten Sticht, Alexander Marx, Ralf Hofheinz, Stefan Post, Peter Kienle, Philipp Ströbel
BACKGROUND: Loss of imprinting (LOI) of the insulin-like growth factor 2 (IGF2) is an early event in the development of colorectal cancer (CRC). Whether LOI of IGF2 denotes a molecular or clinical cancer subgroup is currently unknown. METHODS: Tumor biopsies and paired normal mucosa from 399 patients with extensive clinical annotations were analyzed for LOI and IGF2 expression. LOI status in 140 informative cases was correlated with clinicopathologic parameters and outcome...
October 2016: Journal of Gastroenterology
Mehrdad Payandeh, Masoud Sadeghi, Edris Sadeghi
Colorectal cancer (CRC) metastasis to the thyroid gland is rare. Here we report a 45 yr-old man in western Iran referred to Hematology Clinic, Kermanshah City, Iran in March 2014 with complaint of exertional dyspnea, multi-nodular goiter as well as complaint of exertional dyspnea, and multi-nodular goiter. His history included a low anterior resection of rectum in 9 months ago for a high-risk stage II rectal adenocarcinoma. He did not show clinical signs of hyperthyroidism other than thyroid enlargement...
2016: Iranian Journal of Pathology
V H Veldore, M R Rao, S A Prabhudesai, R Tejaswi, S Kakara, S Pattanayak, N Krishnamoorthy, B N Tejaswini, D Hazarika, A Gangoli, S M Rahman, J Dixit, R Naik, R B Diwakar, C T Satheesh, H P Shashidhara, S Patil, K S Gopinath, B S Kumar
BACKGROUND: One of the genetic alterations implicated in tumor progression in colorectal cancers (CRCs) are abnormalities in Kristen Rat Sarcoma (KRAS) gene. Evaluation of KRAS mutation status is an important prognostic factor and has predictive value in deciding first line therapy based on monoclonal antibodies such as Cetuximab and Panitumumab in metastatic CRCs. MATERIALS AND METHODS: In this retrospective study, we analyzed 7 different somatic mutations in Exon 2 of KRAS gene in 299 unselected incidental CRC patients who visited the hospital for clinical management during the period 2009-2013...
October 2014: Indian Journal of Cancer
Ulrich Nitsche, Fabian Stögbauer, Christoph Späth, Bernhard Haller, Dirk Wilhelm, Helmut Friess, Franz G Bader
BACKGROUND/AIMS: Recent data suggest that tumors of the right and left colon should be distinguished as they differ in clinical and molecular characteristics. METHODS: A total of 1,319 patients who underwent surgical resection for colon cancer (CC) were investigated. Tumors between the ileocecal valve and the hepatic flexure were classified as right CC (RCC), tumors between the splenic flexure and the rectum as left CC (LCC). RESULTS: RCC revealed a higher cause-specific mortality risk (hazard ratio 1...
2016: Digestive Surgery
Charny Park, Sang Yun Ha, Seung Tae Kim, Hee Cheol Kim, Jin Seok Heo, Young Suk Park, Gregory Lauwers, Jeeyun Lee, Kyoung-Mee Kim
Genomic profiles of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are still insufficiently understood, and the genetic alterations associated with drug responses have not been studied. Here, we performed whole exome sequencing of 12 GEP-NETs from patients enrolled in a nonrandomized, open-labeled, single-center phase II study for pazopanib, and integrated our results with previously published results on pancreas (n = 12) and small intestine NETs (n = 50). The mean numbers of somatic mutations in each case varied widely from 20 to 4682...
January 26, 2016: Oncotarget
Guihua Sun, Ya-Wen Cheng, Lily Lai, Tsui-Chin Huang, Jinhui Wang, Xiwei Wu, Yafan Wang, Yasheng Huang, Jinghan Wang, Keqiang Zhang, Shuya Hu, Ji-Rui Yang, Yun Yen
To explore the role of miRNAs in colorectal cancers (CRC), we have deep sequenced 48 pairs of frozen CRC samples, of which 44 pairs produced high quality sequencing data. By using a combined approach of our bias reduction small RNA (smRNA) deep sequencing protocol and Illumina small RNA TruSeq method for sample bar coding, we have obtained data from samples of relatively large size with bias reduced digital profile results. This novel approach allowed us to validate many previously published results using various techniques to profile miRNAs in CRC tissues or cell lines and to characterize 'true' miRNA signatures highly expressed in colon/rectum (CR) or CRC tissues...
January 26, 2016: Oncotarget
Hirofumi Nakayama, Mayumi Yasuhara
We introduce the establishment of a companion diagnostics sub-section of an anatomic pathology department in our mid-sized general hospital. Recent cancer pharmacotherapy targets are growth factor receptors and their associated signal transduction molecules. The presence or absence of mutations in these genes influences the effects of drugs on an individual tumor. Gene polymorphisms of anti-cancer drug metabolism-related enzymes are also closely associated with severe toxicity. Medical oncologists must have knowledge of gene alterations of growth factor receptors and associated signal transduction molecules and polymorphisms of anti-cancer drug metabolism-related enzymes in each case...
July 2015: Rinsho Byori. the Japanese Journal of Clinical Pathology
Paul Lochhead, Reiko Nishihara, Zhi Rong Qian, Kosuke Mima, Yin Cao, Yasutaka Sukawa, Sun A Kim, Kentaro Inamura, Xuehong Zhang, Kana Wu, Edward Giovannucci, Jeffrey A Meyerhardt, Andrew T Chan, Charles S Fuchs, Shuji Ogino
BACKGROUND: Observational data have suggested that intakes of nutrients involved in one-carbon metabolism are inversely associated with risk of colorectal carcinoma and adenomas. In contrast, results from some preclinical studies and cardiovascular and chemoprevention trials have raised concerns that high folate intake may promote carcinogenesis by facilitating the progression of established neoplasia. OBJECTIVE: We tested the hypothesis that higher total folate intake (including food folate and folic acid from fortified foods and supplements) or other one-carbon nutrient intakes might be associated with poorer survival after a diagnosis of colorectal cancer...
November 2015: American Journal of Clinical Nutrition
Qingyang Feng, Li Liang, Li Ren, Jingwen Chen, Ye Wei, Wenju Chang, Dexiang Zhu, Qi Lin, Peng Zheng, Jianmin Xu
BACKGROUND: In colorectal cancer, there are significant differences between synchronous and metachronous distant metastases. However in recent studies, synchronous and metachronous metastases were always lumped together, neglecting their clinical and molecular differences. The mechanism of the latency of metachronous metastases is still unclear. We conducted this study to reveal the relationship between EGFR pathways and metachronous metastases, and try to find efficient predictors. METHODS: PCRs and pyrosequencing were used to detect KRAS, BRAF, PIK3CA and PTEN mutations in primary tumor tissues in a total of 281 patients from 2002 to 2008...
2015: American Journal of Cancer Research
Kazuko Sakai, Junji Tsurutani, Takeharu Yamanaka, Azusa Yoneshige, Akihiko Ito, Yosuke Togashi, Marco A De Velasco, Masato Terashima, Yoshihiko Fujita, Shuta Tomida, Takao Tamura, Kazuhiko Nakagawa, Kazuto Nishio
Somatic mutations in KRAS, NRAS, and BRAF genes are related to resistance to anti-EGFR antibodies in colorectal cancer. We have established an extended RAS and BRAF mutation assay using a next-generation sequencer to analyze these mutations. Multiplexed deep sequencing was performed to detect somatic mutations within KRAS, NRAS, and BRAF, including minor mutated components. We first validated the technical performance of the multiplexed deep sequencing using 10 normal DNA and 20 formalin-fixed, paraffin-embedded (FFPE) tumor samples...
2015: PloS One
Karen Lise Garm Spindler, Niels Pallisgaard, Rikke Fredslund Andersen, Ivan Brandslund, Anders Jakobsen
BACKGROUND: Circulating cell-free DNA (cfDNA) in plasma has shown potential as biomarker in various cancers and could become an importance source for tumour mutation detection. The objectives of our study were to establish a normal range of cfDNA in a cohort of healthy individuals and to compare this with four cohorts of metastatic colorectal cancer (mCRC) patients. We also investigated the prognostic value of cfDNA and analysed the tumour-specific KRAS mutations in the plasma. METHODS: The study was a prospective biomarker evaluation in four consecutive Phase II trials, including 229 patients with chemotherapy refractory mCRC and 100 healthy individuals...
2015: PloS One
Huma Gul Rehana Janjua, Estrid Høgdall, Dorte Linnemann
Hyperplastic polyps (HP) of the colon and rectum were previously considered benign. Newer studies have suggested that colorectal HP are different entities. The aim of this study was to reclassify lesions from a 5-year period previously classified as colorectal HP into traditional hyperplastic polyp (THP), sessile serrated lesions (SSL), and other lesions. All patients were confirmed in the Danish National Pathology Database for the occurrence of metachronous polyps/adenomas, colorectal cancer (CRC), and other gastrointestinal malignancies...
April 2015: APMIS: Acta Pathologica, Microbiologica, et Immunologica Scandinavica
Ju-Xiang Ye, Yan Liu, Yun Qin, Hao-Hao Zhong, Wei-Ning Yi, Xue-Ying Shi
AIM: To investigate gene mutations and DNA mismatch repair (MMR) protein abnormality in Chinese colorectal carcinoma (CRC) patients and their correlations with clinicopathologic features. METHODS: Clinical and pathological information for 535 patients including 538 tumors was reviewed and recorded. Mutation analyses for exon 2 of KRAS gene and exon 15 of BRAF gene were performed by Sanger sequencing except that in 9 tumors amplification refractory mutation system PCR was used...
February 7, 2015: World Journal of Gastroenterology: WJG
Su Young Kim, Eun Ji Choi, Jeong A Yun, Eun Sun Jung, Seung Taek Oh, Jun Gi Kim, Won Kyung Kang, Sung Hak Lee
BACKGROUND: Syndecan-1 (SDC1) is reported to modulate several key processes of tumorigenesis and has variable expression in many cancers. To date, the cause of altered expression has not been elucidated. In this study, we compared SDC1 expression with various clinicopathological parameters and molecular markers to evaluate its clinical significance in colorectal carcinoma. METHODS: We screened for SDC1 expression using immunohistochemistry in 230 surgical specimens of primary colorectal carcinoma from patients consecutively treated between 2008 and 2011 at Seoul St...
2015: International Journal of Medical Sciences
Jing Chen, Fang Guo, Xin Shi, Lihua Zhang, Aifeng Zhang, Hui Jin, Youji He
BACKGROUND: Mutations in KRAS, BRAF and PIK3CA are the most common somatic alterations found in the colorectal cancer (CRC) patients from Western countries; but their prevalence and prognostic value have not been adequately assessed in Asian patients. The aim of this study was to determine the mutation frequencies of these genes in Chinese CRC patients and to investigate their impact on prognosis. METHODS: The sequences of exon 2 of KRAS, exon 15 of BRAF and exons 9 and 20 of PIK3CA were evaluated by PCR and direct sequencing using DNA extracted from formalin-fixed paraffin-embedded (FFPE) tissues from primary CRC tumors of 214 patients (colon/rectum: 126/88)...
2014: BMC Cancer
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