TITLE

A prospective study of circulating mutant KRAS2 in the serum of patients with colorectal neoplasia: strong prognostic indicator in postoperative follow up

AUTHOR(S)
Ryan, B.M.; Lefort, F.; McManus, R.; Daly, J.; Keeling, P.W.N.; Weir, D.G.; Kelleher, D.
PUB. DATE
January 2003
SOURCE
Gut;Jan2003, Vol. 52 Issue 1, p101
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Background and aims: Mutant tumour derived DNA has been detected in the sera of colorectal cancer patients. We investigated if mutant serum KRAS2 was detectable preoperatively in a large group of patients with colorectal neoplasia. A prospective study of 94 patients who underwent putative curative resection for colorectal carcinoma (CRC) was performed to ascertain if serum mutant KRAS2 could be used postoperatively as a disease marker. Methods: Preoperative sera from 78 patients were analysed (group A). Sera from 94 patients were obtained three monthly for up to three years during the postoperative period (group B). Codon 12 and 13 KRAS2 mutations were analysed in matched tumour and serum samples. Results: In the preoperative group (group A), KRAS2 mutation was found in 41/78 (53%) tumours and in 32/78 (41%) preoperative sera. Of 41 tumour KRAS2 mutation positive cases, 31/41 (76%) had an identical serum mutation detectable. In group B, the postoperative follow up group, 60/94 cases were primary tumour KRAS2 mutation positive. Of these 60, 16/60 (27%) became persistently serum mutant KRAS2 positive postoperatively. Ten of 16 (63%) of these developed a recurrence compared with only 1/44 (2%) patients who remained serum mutant negative (odds ratio 71.7 (95% confidence interval 7.7-663.9; p=0.0000). None of 34 tumour mutation negative cases became serum mutant KRAS2 positive postoperatively, despite recurrence in 9/34 patients. The relative hazard of disease recurrence in postoperative serum mutant KRAS2 positive patients was 6.37 (2.26-18.0; p=0.000). Conclusions: Serum mutant KRAS2 can be detected preoperatively in all stages of colorectal neoplasia. Postoperatively, serum mutant KRAS2 is a strong predictor of disease recurrence, stronger even than Dukes' stage of disease, and thus shows potential for use in clinical practice as a marker of preclinical disease recurrence.
ACCESSION #
9758416

 

Related Articles

  • Correction: Genome-Wide Analysis in Human Colorectal Cancer Cells Reveals Ischemia-Mediated Expression of Motility Genes via DNA Hypomethylation.  // PLoS ONE;Oct2014, Vol. 9 Issue 10, p1 

    No abstract available.

  • Isolation of HELAD1, a novel human helicase gene up-regulated in colorectal carcinomas. Ishiguro, Hideyuki; Shimokawa, Takashi; Tsunoda, Tashuhiko; Tanaka, Toshihiro; Fujii, Yoshitaka; Nakamura, Yusuke; Furukawa, Yoichi // Oncogene;9/12/2002, Vol. 21 Issue 41, p6387 

    Presents a study which isolated HELAD1, a novel human helicase gene up-regulated in colorectal carcinomas. Materials and methods; Results; Discussion.

  • Frequent allelic imbalance at the ATM locus in DNA multiploid colorectal carcinomas. Sugai, Tamotsu; Habano, Wataru; Uesugi, Noriyuki; Jiao, Yu-Fei; Nakamura, Shin-ichi; Yoshida, Toru; Higuchi, Taro // Oncogene;9/20/2001, Vol. 20 Issue 42, p6095 

    DNA multiploidy may involve specific DNA ploidy states with respect to genetic alterations such as oncogenes, tumor suppressor gene mutation and microsatellite instability. To clarify the role of DNA multiploidy in colorectal cancer, we analysed allelic imbalance involving the ATM gene,...

  • Disease genetics: Non-invasive monitoring of resistance mutations. Burgess, Darren J. // Nature Reviews Genetics;May2014, Vol. 15 Issue 5, p291 

    The article discusses the study conducted by Mohan et al. which focuses on the analysis of tumour-derived DNA in the blood of patients with colorectal cancer through high-throughput sequencing.

  • A novel MSH2 mutation in a Chinese family with hereditary non-polyposis colorectal cancer. Duo Zheng; Tiegang Li; Xiaoping Liu; Weixin Hu; Hanchun Chen; Yongjia Yang // International Journal of Colorectal Disease;Aug2007, Vol. 22 Issue 8, p875 

    Hereditary non-polyposis colorectal cancer (HNPCC) is one of the most common hereditary colon cancer syndrome accounting for 1–5% of all colorectal cancer cases. Germline mutations in DNA mismatch repair (MMR) genes are associated with the clinical phenotype of HNPCC. Defects in the MSH2...

  • Expression profiling based on graph-clustering approach to determine colon cancer pathway. Xiao-qu Zhu; Mei-lan Hu; Feng Zhang; Yu Tao; Chun-ming Wu; Shang-zhu Lin; Fu-le He // Journal of Cancer Research & Therapeutics;Jul-Sep2013, Vol. 9 Issue 3, p467 

    Context: Colorectal cancer is the second leading cause of cancer deaths worldwide. DNA microarray-based technologies allow simultaneous analysis of expression of thousands of genes. Aim: To search for important molecular markers and pathways that hold great promise for further treatment of...

  • Circulating cell-free DNA in serum as a biomarker for diagnosis and prognostic prediction of colorectal cancer. Hao, T B; Shi, W; Shen, X J; Qi, J; Wu, X H; Wu, Y; Tang, Y Y; Ju, S Q // British Journal of Cancer;10/14/2014, Vol. 111 Issue 8, p1482 

    Background:To verify whether the concentrations and integrity index of circulating cell-free DNA (ccf-DNA) in serum may be clinically useful for the diagnosis and progression monitoring of colorectal cancer (CRC) patients.Methods:Serum samples were collected from 104 with primary CRC, 85 with...

  • Next-generation sequencing for genetic testing of familial colorectal cancer syndromes. Simbolo, Michele; Mafficini, Andrea; Agostini, Marco; Pedrazzani, Corrado; Bedin, Chiara; Urso, Emanuele D.; Nitti, Donato; Turri, Giona; Scardoni, Maria; Fassan, Matteo; Scarpa, Aldo // Hereditary Cancer in Clinical Practice;8/21/2015, Vol. 13, p1 

    Background: Genetic screening in families with high risk to develop colorectal cancer (CRC) prevents incurable disease and permits personalized therapeutic and follow-up strategies. The advancement of next-generation sequencing (NGS) technologies has revolutionized the throughput of DNA...

  • Comparison of Genetic and Epigenetic Alterations of Primary Tumors and Matched Plasma Samples in Patients with Colorectal Cancer. Danese, Elisa; Minicozzi, Anna Maria; Benati, Marco; Montagnana, Martina; Paviati, Elisa; Salvagno, Gian Luca; Lima-Oliveira, Gabriel; Gusella, Milena; Pasini, Felice; Lippi, Giuseppe; Guidi, Gian Cesare // PLoS ONE;May2015, Vol. 10 Issue 5, p1 

    Background: Although recent advances in circulating DNA analysis allow the prediction of tumor genomes by noninvasive means, some challenges remain, which limit the widespread introduction of cfDNA in cancer diagnostics. We analyzed the status of the two best characterized colorectal cancer...

  • Crowd control in the crypt. Booth, Catherine; Brady, Gerard; Potten, Christopher S. // Nature Medicine;Dec2002, Vol. 8 Issue 12, p1360 

    Presents a study which examined the molecular events that hold crypt cells in their place in the intestines, preventing colorectal cancer. Methods; Results; Conclusions regarding the role of the DNA-binding protein known as T-cell factor.

Share

Read the Article

Courtesy of VIRGINIA BEACH PUBLIC LIBRARY AND SYSTEM

Sign out of this library

Other Topics