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Scientists discover lung cancer mutation that may be responsive to immunotherapies

May 10, 2016, 16:38 UTC+3 MOSCOW

Lung cancer is the most common cancer worldwide leading in the number of deaths

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© Ruslan Shamukov/ITAR-TASS

MOSCOW, 10 May. /TASS /. Researchers from several major US universities and the St. Petersburg State University of Information Technologies, Mechanics and Optics (ITMO) have identified a number of new mutations in lung cancer cells that may be responsive to genomically targeted therapies and to immunotherapy, the ITMO press-service said on Tuesday.

"We have identified several distinct recurrent mutations that are likely to be recognized by the immune system and therefore would be strong candidates for cancer vaccines," said Joshua Campbell, postdoctoral associate at Broad Institute of MIT and Harvard.

"The immune system is highly selective; we simply need to suggest our organism that it didn't notice something really important," said Anton Aleksandrov, researcher at ITMO University involved in software development for the immunological study.

"Cells constantly provide protein pieces called epitopes to the immune system for review. If for some reason, the immune system is not able to capture the epitope of a mutated protein and misses it, the tumor may arise," he said. "The search for epitopes that can be detected by the immune system of a patient is critical to the development of individual treatment strategies for cancer. Attached to proteins, neoepitopes will prompt the immune system where its help is needed."

Lung cancer is the most common cancer worldwide leading in the amount of deaths. Each year, more than 1.5 million cases of lung cancer are registered, of which 85% pertain to two subtypes: lung adenocarcinoma and lung squamous cell carcinoma. Scientists examined 1,144 genome profiles of cancers from patients with lung adenocarcinoma and lung squamous cell carcinoma and found novel driver mutations that affect the activity of several proteins responsible for signaling in cells that provoke tumor growth.

Previously, researchers assumed major driver mutations to be similar between lung adenocarcinoma and lung squamous cell carcinoma, but it is not true. In a new research scientists have detected 38 significantly mutated genes in lung adenocarcinoma and 20 mutant genes in lung squamous cell carcinoma. It was shown, that only 6 mutated genes were shared by both types of tumors. The comparison of discovered genome variants with the other 19 cancer types have showed that lung squamous cell carcinoma is more similar to head and neck tumors and to a subset of bladder carcinomas than to lung adenocarcinomas.

The researcher’s analysis additionally identified several neoepitopes -protein fragments that may be recognized by immune system and serve as markers to identify and fight cancer - in most cases of lung cancer. Thus, 47% of lung adenocarcinoma and 53% of lung squamous cell carcinoma samples have at least five predicted neoepitopes suggesting a great potential for immunotherapy - type of treatment aimed at harnessing the patient’s own immune system.

The data obtained in the study have been deposited into the most complete database of genetic alterations in cancer cells - Catalogue Of Somatic Mutations In Cancer (COSMIC). Paper was published in the most recent issue of Nature Genetics.

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