Human Cytogenetic Cancer Markers


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Cytogenetics
Tumor markers now simplified part 1

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  • The Use of Molecular Cytogenetic Techniques for the Identification of Chromosomal Abnormalities?
  • Instrumental Thin-Layer Chromatography.

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Looking for your next opportunity? Just like the identification of the marker chromosome or the identification of the complex karyotypes is important in clinics for the evaluation of the patient prognosis as well as the treatment response, needless to say; fluorescence in situ hybridization FISH is the most suitable and rapid method in the above-mentioned situations.

It gives chance to the rapid analysis of chromosomal aneuploidies in dividing and non-dividing cells. In this chapter, we will discuss the general principles of the chromosomal abnormalities and the molecular cytogenetic techniques that can help the identification of presence or absence of a particular DNA sequence or the evaluation of the number of organization of a chromosome or chromosomal region.

A chromosome is the condensed version of the DNA, and it contains two sister chromatids. The critical parts are consisted of centromere, telomere and nucleolar organizing regions [ 1 ].

Cytogenetics

Depending on the mechanism, chromosomal abnormalities can be classified under two-major groups, numerical and structural abnormalities. The non-disjunction of chromosomes or anaphase lagging is the major cause of the numerical chromosome abnormalities. The structural abnormalities can be classified as balanced and unbalanced abnormalities.

Balanced structural abnormalities include translocations, insertions and inversions. Unbalanced structural abnormalities include deletions, duplications, marker and ring chromosomes [ 2 , 3 ]. The identification of these numerical and structural abnormalities has an impact on the diagnosis of the syndromes, understanding of the phenotypic effects of chromosomal abnormalities, identification of the diagnosis and prognosis of haematological malignancies or solid tumours [ 3 ].

From that perspective, one can say that the identification of chromosome abnormalities has an important role in several conditions. The diagnosis of chromosomal abnormalities is the most important factor in haematology, prenatal genetics and postnatal diagnosis of genetic conditions [ 4 — 6 ]. Chromosomal abnormalities involve the pathogenesis of several clinical conditions like infertility or hematologic malignancies and are important indicators for their diagnosis and prognosis [ 4 , 5 , 7 ]. There are a several methods that can be used to detect the genetic changes in genetic clinics include: conventional cytogenetics karyotyping on cells derived from cell cultures using banding analysis; G-banding ;.

Conventional cytogenetics is the golden standard and most comprehensive method to assess chromosomal abnormalities, especially numerical and structural chromosome aberrations. This chapter summarizes the structural abnormalities and the use of molecular cytogenetics as well as the identification of the chromosomal abnormalities. Chromosomal analysis can be used as a golden standard for pre-natal and post-natal genetic diagnostic testing. In prenatal diagnosis, prenatal chromosomal analysis is applied during the following conditions. Presence of structural chromosomal or genome abnormality in one of the parents.

Stillbirth or neonatal deaths [ 2 ]. Postnatally chromosome analysis is applied during the following conditions: Fertility problems. Deletions of 5q, monosomy 7, deletion of 7q, trisomy 8, deletion of 9q, trisomy 11, trisomy 13, and trisomy 1 are the unbalanced abnormalities in AML. Acute myeloid leukaemia with associated abnormalities of 11q23 has an intermediate survival. The MLL gene at 11q23 is involved in a number of translocations with different partner chromosomes. The more common translocations observed in childhood AML are t 9;11 p21;q23 and t 11;19 q23;p Understanding the role of chromosomal abnormalities in the pathogenesis of haematological malignancies led to the development of a selective treatment options and gives prognosis information [ 13 , 16 — 20 ].

The development fluorescence in situ hybridization FISH technique increased the resolution of visualization of the chromosome rearrangements which is at the submicroscopic level [ 12 , 21 ]. The FISH is applied on metaphase chromosomes, interphase nuclei, fixed tissues or cells and solid tumour samples [ 22 ].

For FISH analysis, epifluorescence microscopes with specific filters and for identifying fluorochromes, a charge-coupled device CCD camera that captures the images were needed. A huge range of probes can be used for the identification of the chromosome abnormalities, which includes whole-chromosome painting probes, chromosome-arm painting probes, repetitive centromeric, subtelomeric and locus-specific probes [ 24 ]. These techniques give chance to the simultaneous visualization and the detection of all human chromosomes.

These three FISH techniques use similar probes to be able to stain each of the 24 human chromosomes with a different colour [ 38 ]. Another high-resolution molecular cytogenetic technique for metaphase chromosomes, which gives chance to analyse chromosomes, is called multicolour banding MCB. This technique involves the microdissection of chromosomal loci to obtain a set of probes that produce multi-colour pseudo-G-banding [ 39 ]. Fluorescent in situ hybridization FISH was used for mapping human genes [ 40 — 43 ], and today, this technology is utilized for the characterization of chromosomal rearrangements and marker chromosomes [ 25 , 44 ], the detection of microdeletions [ 45 ], and the prenatal diagnosis of common aneuploidies [ 46 , 47 ], the detection of prognostic or predictive chromosomal abnormalities in haematological malignancies in clinical cytogenetic laboratories.

At the same time, numerous DNA probes have been commercialized, further promoting the wide-spread clinical applications of molecular cytogenetic. With the current FISH techniques, deletion or rearrangement of a single gene can be detected, cryptic chromosome translocations can be visualized, the copy number of oncogenes amplified in tumour cells can be assessed, and very complex rearrangements can be fully characterized.

RESULTS AND DISCUSSION

Using interphase FISH, genomic alterations can be studied in virtually all types of human tissues at any stage of cell division, without the need of cell culture and chromosome preparation. In that case, FISH is a unique technique that gives way to identification of numerical or structural chromosomal abnormalities in 1—3 days. Depending on the suspected genetic abnormalities type, the FISH probes can be generally subclassified into the following categories: Centromere-specific probes.

Translocation fusion probes [ 58 ]. Translocation involves the exchange of chromosome segments between two chromosomes [ 2 ]. The balanced reciprocal translocation carrier individuals are clinically normal; they do have an increased risk for having children with unbalanced karyotypes secondary to meiotic non-disjunction of their translocation [ 1 ].

In addition to being inherited, reciprocal translocations can also occur as new or de novo mutations and can be disrupt the proto-oncogenes and can cause uncontrolled cell division and cancer development. The identification of translocations is mostly used for the evaluation of the haematopoietic malignancies.

There are two types of probes, which are used to detect translocations: single- or dual- fusion probes and break-apart probes. A dual-fusion probe consists of a pair of probes labelled with two different colours fluorochromes , green e.

Clinical and Cytogenetic Analyses in Uveal Melanoma | IOVS | ARVO Journals

FITC and red e. Gaasenbeek et al. Lips et al. Furthermore, Lips et al. They found five specific chromosomal aberrations that could discriminate between adenoma and carcinoma. Sheffer et al. They tested SNP array profiles from different types of tissue normal, adenoma, different stages CRC and metastasis. They found deletions of 8p, 4p and 15q to be associated with progression of CRC and poor survival outcome. In contrast to the previous studies, with paired and much larger sample size from a homogenous group of 86 CRC patients, our present study aimed to detect chromosomal aberrations using Illumina's Infinium based high-density k and k SNP array.

Human Cytogenetic Cancer Markers Human Cytogenetic Cancer Markers
Human Cytogenetic Cancer Markers Human Cytogenetic Cancer Markers
Human Cytogenetic Cancer Markers Human Cytogenetic Cancer Markers
Human Cytogenetic Cancer Markers Human Cytogenetic Cancer Markers
Human Cytogenetic Cancer Markers Human Cytogenetic Cancer Markers
Human Cytogenetic Cancer Markers Human Cytogenetic Cancer Markers
Human Cytogenetic Cancer Markers Human Cytogenetic Cancer Markers
Human Cytogenetic Cancer Markers Human Cytogenetic Cancer Markers
Human Cytogenetic Cancer Markers

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