Identifying mutated genes
Malignant melanoma, a type of skin cancer, is due to the uncontrolled division of melanocytes, melanin-producing cells. Mutations in one or the other of at least three genes involved in signalling pathways have been reported to be involved in the uncontrolled growth of these cells. Identifying which gene is mutated can help us develop more precise treatments for melanomas. However, studies on mutations in Indian populations with melanomas are limited.
So researchers from the Homi Bhabha National Institute, Mumbai recently examined the frequency of such mutations and their clinical outcomes in India.
In global data, 50% of melanoma cases are seen to have mutations in the BRAF gene, which codes for a kinase responsible for the transduction of the signals from outside to the nucleus of the cell, to initiate cell division. Another 25% of the mutations are seen in the NRAS gene, which encodes for another signal transduction gene stimulating cell proliferation. The researchers decided to look for the presence of these two prominent mutations among Indian melanoma patients.
The department of pathology of the Homi Bhabha National Institute had 88 hematoxylin and eosin stained microscopic slides of melanoma cases registered in a tertiary cancer referral centre from 2001 to 2008. The researchers reviewed the slides to reconfirm the tumour.
From hospital records, they found that many patients were from the western parts of India, but there were patients from the east, north, and south also. The melanoma patients were between 13 and 79 years of age. Males were more common than females.
The researchers obtained 74 melanoma tissue biopsy samples. From the samples, they isolated and sequenced the DNA of BRAF and NRAS genes. Comparing these sequences with sequences from healthy individuals available in databases, the researchers identified mutations in the two genes.
More than half the patients with BRAF mutations were from the eastern parts of the country, and half the patients with mutations in the NRAS gene were from the western parts. Patients from the south and north did not have mutations in either gene.
Only 16% of Indian melanoma patients had mutations in the BRAF gene compared to 50% of patients worldwide. About 15% had mutations in the NRAS gene. Again, lower than the global average of 25%.
Mutations in these two genes are usually mutually exclusive. However, two patients in the cohort carried mutations in both genes. The coexistence of the mutations in these genes could be due to the accumulation of mutations in cancer cells over time, say the researchers.
The researchers were surprised to find that only less than one-third of the patients had the two mutations instead of three-fourths as expected from global data.
Meanwhile, they have other interesting results to report. There are three marker proteins used for the diagnosis, identification of stage, and monitoring of cancers: HMB45, S100P, and Melan A proteins. The researchers used fluorescent antibodies against these proteins to detect the presence and levels of these proteins in the samples. There was indeed an association of these marker proteins along with mutations in the BRAF and NRAS genes. However, not in all cases. So the direct detection of mutations in the likely genes will need to be done to diagnose the root cause in melanoma cases.
Besides BRAF and NRAS, mutations in the gene for neurofibromin, a tumour suppressor, are also known to be involved in melanoma. Mutations in these genes are seen in some other types of cancers as well.
About two million cases of cancers were diagnosed in 2022 and there were more than six lakh deaths. Identifying all genes involved in cancers, developing easy technologies to identify the mutations and developing targeted therapies may soon bring these numbers down.
South Asian Journal of Cancer 2023;
DOI: 10.1055/s-0043-1760759
Reported by A Anuradha
Andhra Medical College, Visakhapatnam
*This report was written during the fourth online workshop on science writing organised by Current Science.
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