scholarly journals Relationship between genetic alterations and prognosis in sporadic colorectal cancer

2006 ◽  
Vol 118 (7) ◽  
pp. 1721-1727 ◽  
Author(s):  
Shih-Ching Chang ◽  
Jen-Kou Lin ◽  
Shung Haur Yang ◽  
Huann-Sheng Wang ◽  
Anna Fen-Yau Li ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Genetic Alterations ◽  
Sporadic Colorectal Cancer

scholarly journals Tracking the Antibody Immunome in Sporadic Colorectal Cancer by Using Antigen Self-Assembled Protein Arrays

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2718
Author(s):  
María González-González ◽  
José María Sayagués ◽  
Luis Muñoz-Bellvís ◽  
Carlos Eduardo Pedreira ◽  
Marcello L. R. de Campos ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Clinical Utility ◽  
Genetic Alterations ◽  
Western World ◽  
Sporadic Colorectal Cancer ◽  
Protein Arrays ◽  
Humoral Immune ◽  
Cellular Processes ◽  
Healthy Donors ◽  
Associated Proteins

Sporadic Colorectal Cancer (sCRC) is the third leading cause of cancer death in the Western world, and the sCRC patients presenting with synchronic metastasis have the poorest prognosis. Genetic alterations accumulated in sCRC tumor cells translate into mutated proteins and/or abnormal protein expression levels, which contribute to the development of sCRC. Then, the tumor-associated proteins (TAAs) might induce the production of auto-antibodies (aAb) via humoral immune response. Here, Nucleic Acid Programmable Protein Arrays (NAPPArray) are employed to identify aAb in plasma samples from a set of 50 sCRC patients compared to seven healthy donors. Our goal was to establish a systematic workflow based on NAPPArray to define differential aAb profiles between healthy individuals and sCRC patients as well as between non-metastatic (n = 38) and metastatic (n = 12) sCRC, in order to gain insight into the role of the humoral immune system in controlling the development and progression of sCRC. Our results showed aAb profile based on 141 TAA including TAAs associated with biological cellular processes altered in genesis and progress of sCRC (e.g., FSCN1, VTI2 and RPS28) that discriminated healthy donors vs. sCRC patients. In addition, the potential capacity of discrimination (between non-metastatic vs. metastatic sCRC) of 7 TAAs (USP5, ML4, MARCKSL1, CKMT1B, HMOX2, VTI2, TP53) have been analyzed individually in an independent cohort of sCRC patients, where two of them (VTI2 and TP53) were validated (AUC ~75%). In turn, these findings provided novel insights into the immunome of sCRC, in combination with transcriptomics profiles and protein antigenicity characterizations, wich might lead to the identification of novel sCRC biomarkers that might be of clinical utility for early diagnosis of the tumor. These results explore the immunomic analysis as potent source for biomarkers with diagnostic and prognostic value in CRC. Additional prospective studies in larger series of patients are required to confirm the clinical utility of these novel sCRC immunomic biomarkers.

PORCINE MODELS FOR HUMAN CANCER

2013 ◽  
Vol 25 (1) ◽  
pp. 321 ◽  
Author(s):  
Tatiana Flisikowska ◽  
Simon Leuchs ◽  
Anja Saalfrank ◽  
Stefan Eser ◽  
Alexander Kind ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Human Cancer ◽  
Genetic Alterations ◽  
Sporadic Colorectal Cancer ◽  
Tumour Suppressor Genes ◽  
Adenomatous Polyposis ◽  
Human Cancers ◽  
Human Scale ◽  
Valuable Adjunct ◽  
Genetically Engineered Mice

Cancers are a leading cause of death worldwide and a major priority for biomedical research. Most animal models of solid cancers are in rodents, particularly genetically engineered mice. However, mice differ significantly from humans in size, lifespan, physiology, anatomy, and diet, limiting their usefulness for some studies. Pigs are increasingly recognised as a valuable adjunct to pre-clinical research. Our aim is to provide a series of genetically defined pigs that model serious and common human cancers. These will allow new diagnostic and therapeutic strategies to be investigated at human scale, and longitudinal studies under conditions that mimic the human patient. We are thus engaged in a program of gene targeting to replicate in pigs a series of genetic lesions known to underlie human cancers. Here, we describe results from two key tumour suppressor genes: adenomatous polyposis coli (APC) and p53 (TP53). Somatic mutations resulting in inactivation or altered p53 function are present in most human cancers, and germline TP53 mutations are responsible for Li-Fraumeni multiple cancer syndrome. TP53R175H is the most frequent missense mutation in many sporadic human cancers. We have created gene-targeted knockout pigs and pigs carrying a latent TP53R167H mutant allele orthologous to human mutant TP53R175H that can be activated by Cre recombination to model the occurrence of oncogenic mutant p53 in chosen tissues (Leuchs et al. 2012 PLoS One, in press). In vitro studies indicate that porcine TP53R167H resembles human TP53R175H in altered function, and homozygous knockout of porcine TP53 results in transformation of porcine MSCs. APC plays a vital initiating role in both sporadic colorectal cancer (CRC) and the inherited predisposition to colorectal cancer, familial adenomatous polyposis (FAP). We generated gene-targeted cloned pigs carrying two different nonsense mutations in APC (APC1061 and APC1311) at sites orthologous to human germline mutations responsible for FAP. At 1 year of age, the APC1311 mutation resulted in >100 lesions, including ~60 polyps, exclusively in the large intestine. Importantly, this accords with the location and onset of human FAP in early adulthood, and contrasts with equivalent mutations in mice where polyps develop in the small intestine. Histological and molecular analysis showed that the porcine model recapitulates all major features of early stage human FAP (Flisikowska et al. 2012 Gastroenterology, in press). Tumorigenesis involves multiple genetic alterations over time. It will now be possible to mimic this progression in pigs by combining these and other mutations. We are confident that pig models will make a significant contribution to human oncology.

scholarly journals Microsatellite Instability and Loss of Heterozygosity of Tumor Suppressor Genes in Bosnian Patients with Sporadic Colorectal Cancer

2008 ◽  
Vol 8 (4) ◽  
pp. 313-321
Author(s):  
Vesna Hadžiavdić ◽  
Nada Pavlović-Čalić ◽  
Izet Eminović
Keyword(s):  
Colorectal Cancer ◽  
Tumor Suppressor ◽  
Microsatellite Instability ◽  
Tumor Suppressor Genes ◽  
Genetic Alterations ◽  
Sporadic Colorectal Cancer ◽  
Tumor Type ◽  
Suppressor Genes ◽  
Amsterdam Criteria ◽  
Surrounding Healthy Tissue

Considering its frequency, high mortality rate as well as many etiological mysteries colorectal cancer is a challenge to contemporary science. In our study we analyzed RER + and RER - phenotypes and their relations with clinical-pathological characteristics of sporadic colorectal cancers. We also analyzed genetic alterations of tumor suppressor genes as well as their relation with microsatellite instability. The study was based on 54 tumor samples and 54 samples of the surrounding healthy tissue of patients with colorectal cancer. According to Amsterdam Criteria and Bethesda Criteria 35/54 or 64,81% belonged in the group of sporadic colorectal cancer. Mononucleotide marker Bat 25 showed instability in 48,57%; Bat 26 in 45,71% and Bat 40 in 29/35 82,86% of tumor samples. Considering dinucleotide markers, TP 53 showed instability in 54,29% and DS123 in 37,14% of tumor samples. Genetic alterations in tumor suppressor genes were found in tumor tissue: NM 23 in 54,29% samples, p53 in 51,43%, APC in 51,43%, DCC2 in 34,29%, RB1 in 22, 86% and DCC 1 in 28,57%. Our studies confirmed that genetic instability had an important role in the development of tumor type. Our results showed that mononucleotide marker Bat 40 might be used for an easy and fast screening procedure in Bosnian population, because it exhibited high percent of microsatellite instability and was in relation with RER+ phenotype. This investigation showed that different genetic alterations may occur during cancer development in each individual patient’s tumor. These changes result in MMR inactivation, which causes RER+ phenotype. Our results suggest a connection between alteration in some tumor suppressor genes and MSI phenotype of sporadic colorectal cancer in Bosnian population.

Clinicopathologic Features of Sporadic Colorectal Cancer with MLH1/MSH2 Loss of Expression - Reduced Likelihood of Metastases

2008 ◽  
Vol 24 (3) ◽  
pp. 175 ◽  
Author(s):  
Ji Won Park ◽  
Hee Jin Chang ◽  
Kyung Hae Jung ◽  
Dae Yong Kim ◽  
Dae Kyung Sohn ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Sporadic Colorectal Cancer ◽  
Clinicopathologic Features
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