Genetic Variants of Selected Genes in Colo-Rectal Cancer Patients.

Study Overview
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Brief Summary
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Colorectal cancers (CRC) are the third most common human malignancy, and are also the leading cause of cancer related deaths worldwide. Early detection of premalignant lesions such as adenomatous polyps has decreased the risk of CRCs; however, cases which are initially undetected and progress to advanced CRC with distant metastasis are still unfortunately incurable. The development of CRC is a complex and heterogeneous process arising from an interaction between multiple etiological factors, including genetic factors and environmental factors such as diet and lifestyle. The challenges are to understand the molecular basis of individual susceptibility to colorectal cancer and to determine factors that initiate the development of the tumor, drive its progression, and determine its responsiveness or resistance to antitumor agents. Next generation sequencing(NGS)-driven genomic studies are already reporting novel features of cancer genomes beyond the traditional mutational categories. Recent advance in sequencing technology has enabled comprehensive profiling of genetic alterations in CRC.These methods are facilitating an increase in the efficiency and resolution of detection of each of the principal types of somatic cancer genome alterations, including nucleotide substitutions, small insertions and deletions, copy number alterations, chromosomal rearrangements,DNA methylation sequencing such as bisulfite-sequencing and microbial infections. Besides the microsatellite instability (MSI), some researchers reported novel mitochondrial mutations in the cancer genomes. NGS technology will help the investigators for understanding of entire CRC genomes and the obtained knowledge will lead to a better diagnosis and personalized targeted therapeutics for CRC management

Detailed Description
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Identification of the problem:Colorectal cancers (CRC) are the third most common human malignancy, and are also the leading cause of cancer related deaths worldwide. Early detection of premalignant lesions such as adenomatous polyps has decreased the risk of CRCs; however, cases which are initially undetected and progress to advanced CRC with distant metastasis are still unfortunately incurable. The development of CRC is a complex and heterogeneous process arising from an interaction between multiple etiological factors, including genetic factors and environmental factors such as diet and lifestyle. The challenges are to understand the molecular basis of individual susceptibility to colorectal cancer and to determine factors that initiate the development of the tumor, drive its progression, and determine its responsiveness or resistance to antitumor agents. Next generation sequencing(NGS)-driven genomic studies are already reporting novel features of cancer genomes beyond the traditional mutational categories. Recent advance in sequencing technology has enabled comprehensive profiling of genetic alterations in CRC.These methods are facilitating an increase in the efficiency and resolution of detection of each of the principal types of somatic cancer genome alterations, including nucleotide substitutions, small insertions and deletions, copy number alterations, chromosomal rearrangements,DNA methylation sequencing such as bisulfite-sequencing and microbial infections. Besides the microsatellite instability (MSI), some researchers reported novel mitochondrial mutations in the cancer genomes.NGS technology will help the investigators for understanding of entire CRC genomes and the obtained knowledge will lead to a better diagnosis and personalized targeted therapeutics for CRC management.Experimental design: The study design to attempt to identify the unique mutational spectrum and novel targets of genomic, epigenetic alterations in Egyptian colorectal cancer patients in Delta Regionusing Whole Exome and Epigenetic deep sequencing.Expected results:NGS-based genome analysis facilitates the identification of unrecognized gene mutation of Egyptian CRC cancer especially in Delta Region which may be biologically different from Western CRC as the environmental factors are different.Significance of the expected results:The results of this project will benefit in(1) Identification of novel features or mutation types in CRC genomes In Delta Region. (2) Understanding the advancement of pathway-level in colorectal carcinogenesis and (3) Identify Clinically relevant genetic and epigenetic biomarkers for noninvasive diagnosis and clinically actionable targets for personalized targeted medicine.

Official Title
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Genetic Variants of Selected Genes Using Target Deep Sequencing in Colo-Rectal Cancer Patients.

Conditions
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Cancer Colon

Intervention / Treatment
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* Genetic: Whole genome sequencing


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ages Eligible for Study: 10 Years and older Genders Eligible for Study: Both Patients who can give informed consent themselves 10 healthy controls will also be included in the study. Exclusion Criteria: Other cancer types rather than CRC. Younger age than 10 years

Ages Eligible for Study
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Minimum Age: 10 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Cancer colon with no distant metastasis<br>Genetic: Whole genome Sequencing | Genetic: Whole genome sequencing<br>* At least 50 ng of tumor DNA will be extracted from FFPE samples and/or fresh tissue and used for hybridization capture and NGS using the IlluminaMiSeqDx platform.<br>|
| Cancer colon with distant metastases<br>Genetic: Whole genome Sequencing | Genetic: Whole genome sequencing<br>* At least 50 ng of tumor DNA will be extracted from FFPE samples and/or fresh tissue and used for hybridization capture and NGS using the IlluminaMiSeqDx platform.<br>|
| control group<br>Genetic: Whole genome Sequencing | Genetic: Whole genome sequencing<br>* At least 50 ng of tumor DNA will be extracted from FFPE samples and/or fresh tissue and used for hybridization capture and NGS using the IlluminaMiSeqDx platform.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of cancer patients with abnormal genetic mutations . | Number of cancer patients having abnormal genetic mutations . | 2 years |