Estimation and Regulation of DNA:
The Future Tool for Diagnosis, Treatment and Prognostic Evaluation of Cancer
- Part 2 -

JC Sanasam *

...Does the DC construct an IB for every village and stay at least five days a month there? Does anybody establish a press and publish a daily newspaper at a remote corner where the population is only 100, where there is no electricity and where no bus, no vehicle can reach?

To understand more about the role of DNA in diseases and cancer we got to have some knowledge about the Human Genome Project, DNA mapping, so and so forth.

The US Department of Energy and the National Institutes of Health began the Human Genome Project (HGP) in 1990 - its aims are to determine the sequence of all 3 billion base pairs in human DNA and identify every one of our genes. The Wellcome Trust UK was a major partner during the early years; contributions came from Japan, France, Germany, China and others as well.

In February 2001 the first of these objectives was achieved, at least in working draft form. The target of the final version was 2004 but it was completed by 2003, one year ahead, a matter of 13 years only. By licensing the technology to private companies and awarding grants for innovative research the project catalyzed the multi-billion dollar US Biotechnology industry and fostered development of new medical applications.

DNA mapping and sequencing the Human Genome, the primary goal of the project, is to make a series of descriptive diagrams of maps of each human chromosome at increasingly finer resolution. Mapping involves: 1) dividing the chromosomes into smaller fragments that can be propagated and characterized; 2) ordering (mapping) them to correspond to their respective locations. After mapping, the next step is to determine the base sequence (of the pairs of adenine, thymine, guanine and cytosine) of each of the ordered DNA fragments.

The ultimate goal of genome research is to find all the genes in the DNA sequences and to develop tools for using this information in the study of human biology and medicine. Improving the instrumentation and technique required for mapping and sequencing, which is a major focus of the project, has now proved to have increased the efficiency and cost effectiveness. Goals include also automating methods and optimizing techniques to extract the maximum useful information from maps and techniques.

A genome map describes the order of genes or other markers and the spacing between them on each chromosome. Such human genome maps are constructed on several scales and levels of resolution for more detailed study, applications and biological scientific interpretations. At the coarsest resolution are genetic linkage maps, which depict the relative chromosomal locations of DNA markers (genes and other identifiable DNA sequences) by their pattern of inheritance. Physical maps describe the chemical characteristics of the DNA molecule itself.

Geneticists have already charted the approximate positions of over 2300 genes and a start has been made in establishing high resolution maps of gene, for convenience and clarity in identification and interpretations.

The DNA mapping can be copied or alterations in DNA methylation, gene expression, gene transcriptions, and epigenetic configuration can be read pertinent to applied studies and extraction of interpretation and information.

DNA methylation is an important regulator of gene transcription, and its role in carcinogenesis (birth of cancer) has been a topic of considerable interest in the last decade.

Alterations in DNA methylation are commonly seen in a variety of tumors malignant (dangerous and capable of killing the patient) or non malignant. DNA hypermethylation is found to be consistently associated with many cases of leukemias and other hematological (blood related) cancers and diseases. Hypermethylation of p15 gene has been found in 65% of blood related malignancies where there is degeneration of bone marrow which usually is very malignant with lower survival and results into transformation to acute myeloid lukemia. On the other hand the presence of hypermethylation of the p21 gene is associated with cases of acute lymphoblastic leukemia.

Hypomethylation is another kind of methylation defect that is observed in a wide variety of malignancies, like the solid tumor of metastatic hepatocellular (liver) cancer, hematological (related to blood) malignancies such as B-cell chronic lymphocytic leukemia, and also in breast, cervical (neck of the womb), lung, brain cancers etc. Hypomethylation of the mobile DNA again is found in cases of bladder and colon malignancies. In this way geneticists are working hard to find and identify which defective gene is there and where it is for every case of cancer.

Obtaining such knowledge, now geneticists can do lots of things in matters of early detection and diagnosis of cancers; talk better about the stage, progress and severity; and administer the innovative gene therapy in the form of gene alteration or gene activation or gene replacement or gene suppression or gene silencing etc. as treatment of various cancers according to what is required from case to case.

To deal with the rest of the things where DNA and gene can play their roles in the prognostic evaluation and therapeutic management of cancers I am afraid it will ask for a larger space. These have to follow with the next week's write up.

Another sad thing is that Manipur seems to take plenty of time to catch up with, be familiar with and practically apply the knowledge of new inventions, discoveries and procedures that keep popping out every day in the world of medicine. Things will reach Manipur last, years after, when the thing is already completed worldwide.

Medical science is growing in leaps and bounds and those in the tribe are supposed to have visions beyond. Medical scientists of Manipur seem to take only a lukewarm interest towards such innovative progresses maybe because they have no money on their own to rush to the upcoming centres and pick up the stuff or maybe, even if they do so, there would be no scope of doing anything in that line back at home. Manipur is more interested in killing, collection of forced money.

The government on the other hand is busy supplying high voltage X-ray machines, ultra sound and CT machines at centres where there is no electricity, sending doctors where there is not a single construction even to the status of a shed as the health centre building; and dump the doctor there years together. Doctors, especially the modern ones, are human beings after all. If no society is around him, at least he would require a TV, a mobile set; preferably a laptop and for all these he needs electricity.

What Manipur requires for now in priority is electricity, hygienic water, a road for the bus, preferably the car, to reach the health center at its threshold. We do know doctors are different from journalists or the District IAS officer.

Does the DC construct an IB for every village and stay at least five days a month there? Does anybody establish a press and publish a daily newspaper at a remote corner where the population is only 100, where there is no electricity and where no bus, no vehicle can reach? Sic.

To be continued ...