E-Paper
New research provides efficient approach to early diagnosis of cancer
Scientists have discovered that a nuclear architecture protein, Lamin B Receptor (LBR), plays a role in maintaining chromosomal stability in colorectal cancer cells. The depletion of LBR from these cells resulted in the loss of specific chromosomes. This finding could lead to improved early diagnosis of colorectal and other cancers.
Scientists have taken a step towards an improved approach to early diagnosis of cancer, especially cancers that start as a growth on the inner lining of the colon or rectum.
For the first time, they have found that nuclear architecture protein Lamin B Receptor (LBR) has a direct molecular role in the maintenance and regulation of chromosomal stability in diploid colorectal cancer cells.
As the burden of cancer is increasing at an unprecedented rate, especially in a country such as India with a massively heterogeneous socio-economic stratification with limited access to healthcare for a large majority of our population, it is important to device and deliver appropriate and state of the art and low-cost approaches for the early diagnosis of cancers.
The loss or gain of chromosomes from cells is a defining feature of chromosomal instability (CIN), a hallmark of more than 90% of all cancers.
Interestingly, proteins that maintain nuclear architecture are also required for the maintenance of stable chromosome numbers across cell types.
LBR has a unique function as it is not only a receptor but also an important factor required for the reformation of the nuclear envelope from early to late mitosis.
Noticing this unique feature of LBR, scientists from the Chromosome Biology Lab (CBL) at the Indian Institute of Science Education and Research (IISER), Pune, surmised that LBR is also likely to be involved in the regulation of chromosomal stability.
They closely probed the role of nuclear architecture protein in chromosomal stability.
Kundan Sengupta, professor and associate dean (International Relations and Outreach) Biology at IISER, said, “It is a useful model for early cancer detection as both high and low LBR number is associated with the cancer disease.”
“Although currently, we have focused more on fewer LBR numbers, in the coming time we will also be studying the impact of Higher LBR levels. It is one of those many molecule that needs to be tightly maintained. As of now, we don’t know how this connects with therapy, but in the coming days we will be looking at this aspect as well,” he said.
The study supported by the Science and Engineering Research Board (SERB) an attached institution of the department of science and technology showed that the depletion of LBR from colorectal cancer cells resulted in the loss of specific chromosomes.
These chromosomes also assumed an aberrant and altered 3-dimensional spatial localisation, which correlates with its eviction from the nucleus into nuclear protrusions and micronuclei - a key event in the loss of chromosomes in a targeted manner from the nucleus.
The study published in the journal Human Molecular Genetics revealed a unique network of proteins that are associated with LBR which involves telomere-associated factors (TRF) among others - also essential for the maintenance of chromosomal stability in otherwise diploid human colorectal cancer cells.
On December 20, the department of science and technology also highlighted the significance of this study in early cancer diagnosis.
The team used Fluorescence In Situ Hybridization (FISH), a laboratory technique used to detect and locate DNA sequences of a gene on a chromosome.
Using a technology called Spectral Karyotyping (SKY) that enables the identification of aberrations in every single chromosome by labelling each chromosome with a unique colour, the team of scientists consisting of Shalaka Patil, Shruti Deshpande and Kundan Sengupta uncovered the change in chromosomal numbers in cancer cells.
They discovered for the first time that the depletion of LBR resulted in the loss of specific chromosomes from otherwise diploid colorectal cancer cells.
According to the authors, a careful evaluation of the levels of nuclear architecture proteins such as LBR and TRF is likely to serve as an effective and efficient means for the early diagnostics and detection of not only colorectal but various other cancers that are taking lives at an alarming rate in India and across the world.
