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kras mutation in rectum cancer

Ilufredo Y Tantoy, Anand Dhruva, Janine Cataldo, Alan Venook, Bruce A Cooper, Steven M Paul, Jon D Levine, Yvette P Conley, Frances Cartwright, Kathryn Lee, Fay Wright, Christine Miaskowski
BACKGROUND: Approximately 28% of patients with gastrointestinal (GI) cancers will receive targeted therapy (TT) because of the associated increases in survival. Only four studies have examined the symptom experience of these patients. To date, no studies have evaluated for differences in symptom occurrence, severity, and distress between patients who received chemotherapy (CTX) alone (n=304) or CTX with TT (n=93). METHODS: Patients completed self-report questionnaires, approximately one week after they received CTX...
February 2017: Journal of Gastrointestinal Oncology
Raaj S Mehta, Mingyang Song, Reiko Nishihara, David A Drew, Kana Wu, Zhi Rong Qian, Teresa T Fung, Tsuyoshi Hamada, Yohei Masugi, Annacarolina da Silva, Yan Shi, Wanwan Li, Mancang Gu, Walter C Willett, Charles S Fuchs, Edward L Giovannucci, Shuji Ogino, Andrew T Chan
BACKGROUND & AIMS: Western and prudent dietary patterns have been associated with higher and lower risks of colorectal cancer (CRC), respectively. However, little is known about associations between dietary patterns and specific anatomic subsite or molecular subtypes of CRC. METHODS: We used multivariable Cox proportional hazards models to examine associations between Western and prudent dietary patterns and CRC risk in the Health Professionals Follow-up Study and Nurses' Health Study...
February 26, 2017: Gastroenterology
Mayank Jauhri, Akanksha Bhatnagar, Satish Gupta, Manasa Bp, Sachin Minhas, Yogender Shokeen, Shyam Aggarwal
Colorectal cancer incidences are on a rise in India. In this study, we have analyzed the mutation frequencies of six potential biomarkers, their coexistence, association with clinicopathological characteristics, and tumor location in Indian colorectal cancer patients. Next-generation sequencing was performed to identify mutations in the six potential biomarker genes using formalin-fixed paraffin-embedded tissue blocks of 112 colorectal cancer patients. The mutation frequency observed in KRAS, BRAF, PIK3CA, NRAS, TP53, and APC was 35...
February 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Yu Sunakawa, Wataru Ichikawa, Akihito Tsuji, Tadamichi Denda, Yoshihiko Segawa, Yuji Negoro, Ken Shimada, Mitsugu Kochi, Masato Nakamura, Masahito Kotaka, Hiroaki Tanioka, Akinori Takagane, Satoshi Tani, Tatsuro Yamaguchi, Takanori Watanabe, Masahiro Takeuchi, Masashi Fujii, Toshifusa Nakajima
INTRODUCTION: Primary tumor location is a critical prognostic factor in metastatic colorectal cancer (mCRC); however, it remains unclear whether tumor location is a predictor of the response to cetuximab treatment. It is also uncertain if BRAF mutation contributes to the impact of tumor location on survival. We assessed the prognostic impact of tumor location on clinical outcomes in mCRC patients treated with first-line cetuximab chemotherapy. PATIENTS AND METHODS: The associations of tumor location with overall survival and progression-free survival were evaluated in mCRC patients with KRAS exon 2 wild-type tumors who were enrolled onto 2 clinical trials: JACCRO CC-05 of cetuximab plus FOLFOX (n = 57, UMIN000004197) and CC-06 of cetuximab plus SOX (n = 61, UMIN000007022)...
October 6, 2016: Clinical Colorectal 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
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