Analysis of genomic DNA copy number alterations in chromosome arm 18q demonstrates distinct molecular categories of colorectal carcinoma

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10005-10005
Author(s):  
H. Ji ◽  
M. Zhang ◽  
K. Farnam ◽  
K. Salari ◽  
R. Davis ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colorectal Carcinoma ◽  
Genomic Instability ◽  
Genetic Markers ◽  
New Technologies ◽  
Stage Ii ◽  
Cancer Genes ◽  
Genomic Deletions ◽  
Chromosome Arm ◽  
Dna Copy Number Alterations

10005 Background: Genomic instability is a major feature of neoplastic development in colorectal carcinoma and other cancers. Specific genomic instability events such as genomic deletions have potential utility as biologically relevant prognostic biomarkers. Loss of heterozygosity (LOH) on chromosome arm 18q is an indicator of colorectal carcinoma behavior and potentially, prognosis. For stage II and III colorectal cancer, a number of retrospective studies have shown strong correlations between deletions in 18q and reduced survival. However, other studies have failed to identify this correlation. This discrepancy is likely the result of different sets of genetic markers and their widely disparate locations along chromosome arm 18q, often separated by megabases. New technologies are needed to overcome these issues. Methods: Using a novel genomic technology called molecular inversion probes (MIPs), we analyzed genomic deletions at exon-level resolution in primary colorectal carcinoma. Unlike microsatellite genetic markers, MIPs are not dependent on having informative alleles to discern a LOH event. This enables querying microsatellite genetic markers used in any clinical study. We designed a set of probes to interrogate several hundred individual exons of over two hundred cancer genes with an overall distribution covering all chromosome arms. Also represented were a series of over 100 probes along chromosome arm 18q representing genetic markers used in clinical studies. An analysis was carried out on primary tumor samples from patients with stage II and III disease. Results: We discovered several distinct categories of colorectal carcinomas based upon their profile of 18q genomic deletions and other allelic imbalances. Colorectal carcinoma extent of invasion showed an association with cluster designation which suggests that the multiple genomic instability events influence the invasive behavior of colorectal carcinoma. Conclusions: Colorectal cancer has distinct patterns of 18q genomic deletions, representing a potential molecular classifier. This finding has potential clinical ramifications given the application of 18q LOH events as an indicator for adjuvant treatment in stage II colorectal carcinoma. No significant financial relationships to disclose.

Stratification of patients with colorectal cancer of UICC stage II using prognostic mutations signatures obtained by deep amplicon sequencing of cancer genes.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 377-377
Author(s):  
Andre Rosenthal ◽  
Karsten Ridwelski ◽  
Frank Marusch ◽  
Matthias Pross ◽  
Rene Mantke ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Adjuvant Therapy ◽  
Deep Sequencing ◽  
Predictive Value ◽  
Amplicon Sequencing ◽  
Stage Ii ◽  
Rna Expression ◽  
Uicc Stage ◽  
Cancer Genes ◽  
Primary Tumors

377 Background: Assignment of patients (pts) with UICC-stage II colorectal cancer (CRC) to adjuvant therapy remains controversial. The clinical utility of histo-pathological parameters (pT4, L+, V+) as well as tumor RNA expression signatures like Oncotype Dx Colon Cancer Assay, ColoPrint, or Predictor C is low given their positive predictive value (PPV) of 0.13, 0.22, 0.19, and 0.33, respectively, when adjusted to an incidence of 10% for occurrence of metastatic disease (mets) within 3 years after diagnosis. Methods: We applied deep amplicon sequencing of 48 well-known cancer genes to DNA samples of primary tumors from 173 pts with UICC-stage II CRC using the Illumina MiSeq technology. Patients were selected from a prospective, multicenter clinical diagnostic study named MSKK. More than 6,500 patients with CRC have been recruited into this study conducted by 39 hospitals in Germany. 79 of the 173 pts had progression of disease events within 3 years after R0 resection including 40 pts with mets, 12 pts with local recurrences, and 27 pts with secondary malignancies. 94 pts remained progression-free. Results: Deep sequencing revealed a total of 2,221 sequence variations (SV) including missense, stop, InDel, noncoding, nonsense SV. 401 SV were in COSMIC, 750 SV in normal tissue. The remaining 1471 SV served as basis for development of SV-signatures (SVS) for prediction of progression events in a classical double-nested bootstrap approach in order to generate second order unbiased estimates of performance of SVS, namely sensitivity(S+), specificity (S-), PPV, and negative predictive value (NPV). The best SVS for prediction of metastases contained SV in less than 15 genes and has a S+ of 0.41, S- of 0.93, PPV of 0.40, and NPV of 0.93 (incidence of metastasis: 10%). The best SVS for prediction any progression event has a S+ of 0.33, S- of 0.93, PPV of 0.54, and NPV of 0.84 (incidence for any progression = 20.5%). Conclusions: This deep sequencing based prognostic tissue test with a PPV of 40% and a NPV of 93% represents a milestone over prognostic tests based on RNA expression. The increased PPV leads to more patients being treated correctly with adjuvant therapy.

scholarly journals Prognostic Value and Immunohistochemical Analysis of Mismatch Repair Deficiency in Patients with Stage II and III Colorectal Carcinoma—A Single-Center Study

Medicina ◽  
2020 ◽  
Vol 56 (12) ◽  
pp. 676
Author(s):  
Tijana Denčić ◽  
Miljan Krstić ◽  
Aleksandar Petrović ◽  
Maja Jovičić-Milentijević ◽  
Goran Radenković ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colorectal Carcinoma ◽  
Mismatch Repair ◽  
Prognostic Value ◽  
Young Patients ◽  
Immunohistochemical Analysis ◽  
Stage Ii ◽  
Single Center ◽  
Mmr Deficiency ◽  
Disease Free

Background and objectives: Deficient mismatch repair (MMR) status is associated with good prognosis but poor therapeutic response to adjuvant chemotherapy in patients with colorectal cancer. However, there are some opposed arguments considering therapeutic outcomes in patients with evidenced MMR deficiency in colorectal cancer. The aim of the study was the investigation of prognostic value and immunohistochemical analysis of the MMR-deficiency tumors. Materials and Methods: The study enrolled 104 patients with resected stage II and III colorectal cancer samples from the period 2018–2019. Results: The tumors with deficient MMR status were significantly associated with age up to 50 years and right-sided localization (p < 0.001). During the follow-up period of 22.43 ± 6.66 months, 21 patients (20.2%) died, whereas 14 patients (13.5%) had relapses. The loss of mutL homologue 1/postmeiotic segregation increased 2 (MLH1/PMS2) expression, compared to proficient MMR tumors, was associated with shorter disease-free survival in patients with lymphovascular invasion (p < 0.05), perineural invasion (p < 0.01), stage III (p < 0.05) and high-grade tumor (p < 0.05). Conclusions: This retrospective pilot study of a single-center cohort of patients with stage II and III colorectal cancer highlights the clinical importance of using immunohistochemistry (IHC) analysis as a guide for diagnostic algorithm in a country with limited resources, but with a high prevalence of colorectal carcinoma in the young patients. MMR-deficiency tumors compared with proficient MMR colorectal cancer was not shown to be a significant predictor of disease-free and overall survival.

INVESTIGATION KRAS MUTATION IN CIRCULATION TUMOR DNA IN DIFFERENT STAGES OF COLORECTAL CANCER

2019 ◽  
Vol 65 (5) ◽  
pp. 701-707
Author(s):  
Vitaliy Shubin ◽  
Yuriy Shelygin ◽  
Sergey Achkasov ◽  
Yevgeniy Rybakov ◽  
Aleksey Ponomarenko ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Plasma Volume ◽  
Kras Mutation ◽  
Stage Iv ◽  
Circulating Tumor Dna ◽  
Stage Ii ◽  
Kras Gene ◽  
Kras Mutations ◽  
Droplet Pcr ◽  
Tumor Dna

To determine mutations in the plasma KRAS gene in patients with colorectal cancer was the aim of this study. The material was obtained from 44 patients with colorectal cancer of different stages (T1-4N0-2bM0-1c). Plasma for the presence of KRAS gene mutation in circulating tumor DNA was investigated using digital droplet polymerase chain reaction (PCR). KRAS mutations in circulating tumor DNA isolated from 1 ml of plasma were detected in 13 (30%) patients with cancer of different stages. Of these, with stage II, there were 3 patients, with III - 5 and with IV - 5. Patients who did not have mutations in 1 ml of plasma were analyzed for mutations of KRAS in circulating tumor DNA isolated from 3 ml of plasma. Five more patients with KRAS mutations were found with II and III stages. The highest concentrations of circulating tumor DNA with KRAS mutation were found in patients with stage IV. The increase in plasma volume to 3 ml did not lead to the identification of mutations in I stage. This study showed that digital droplet PCR allows identification of circulating tumor DNA with the KRAS mutations in patients with stage II-IV of colon cancer. The results can be used to determine the degree of aggressiveness of the tumor at different stages of the disease, but not the 1st, and it is recommended to use a plasma volume of at least 3 ml.

Fatty Acid Profile and In Vitro Anticancer Activity of Two Marine Sponge- Associated Bacteria

2020 ◽  
Vol 16 (9) ◽  
pp. 1273-1280
Author(s):  
Giuseppina Tommonaro ◽  
Ali M. El-Hagrassi ◽  
Walid Fayad ◽  
Carmine Iodice ◽  
Kamel H. Shaker ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Fatty Acids ◽  
Fatty Acid ◽  
Colorectal Carcinoma ◽  
Cell Line ◽  
Marine Sponge ◽  
Hct116 Cell ◽  
Associated Bacteria ◽  
Sponge Associated Bacteria ◽  
Human Colorectal Carcinoma

Background: Colorectal cancer represents one of the prominent causes of mortality worldwide in men and women. The objective of this study was to search for new potential anticancer compounds, both in prevention and treatment of colorectal cancer. The anticancer potential of marine bacterial extracts against Human colorectal carcinoma cell line (HCT116) was evaluated as well as the partial identification of bioactive metabolites. Methods: All bacterial extracts were tested for their cytotoxicity against HCT116 cell line by means of MTT assay. The highly cytotoxic dichloromethane extracts of marine sponge-associated bacteria Vibrio sp. and Bacillus sp. were analyzed by GC-MS. Results: Two fractions, Vib3 and Bac3, exhibited a very interesting cytotoxicity against human colorectal carcinoma (HCT116) cell line, with a percentage of cytotoxicity of 96.04 % and 29.48 %, respectively. Discussion: The GC-MS analysis revealed the presence of two major fatty acids, palmitic and oleic acids, in Vib3 fraction and fatty acid esters and phenolic compounds in Bac3 fraction. Conclusion: Based on previous literature, it may be hypothesized that the anticancer activity of bacterial extracts could be, at least partially, to the fatty acids fraction.

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