25 September 2012

Three subtypes of the most common form of ovarian cancer

The data obtained will help predict the response of patients to treatment

The results obtained as part of a new study led by specialists from the Dana Farber Cancer Institute will allow doctors to identify patients with low-grade serous ovarian cancer (the most common type of cancer of this organ) who are most likely to respond to drugs of a certain class.

Low-grade serous ovarian cancer cells are characterized by a high degree of genomic instability. This is manifested by the presence of additional chromosomes in the genome or the absence of whole chromosomes or their fragments. One of the consequences of such instability is the absence of two normal copies of each gene – the loss of heterozygosity, which can occur in cells with genes represented not by two normal copies, but by complexes of a normal copy and a copy containing a mutation. If a normal copy of such a gene is inactivated or mutated, only non-functional copies remain in the cell.

As part of the study, scientists analyzed the cells of ovarian tumor samples using technology that allows identifying single nucleotide polymorphisms (snips – single nucleotide polymorphism, SNP), representing differences in one letter of the genetic code. As a result, all the analyzed samples were divided into three groups, clearly differing in the profile of loss of heterozyosity.

The subtype of the disease, whose cells are characterized by the highest level of damage and deletion (loss of a DNA site) in the 13th chromosome (30-50% of cases), is characterized by the slowest development of resistance to chemotherapy drugs. Such patients live longer without disease progression than patients of the other two groups. In general, all identified groups differed in the susceptibility of patients to certain types of chemotherapy.

According to the authors, the loss of heterozygosity reduces the survival of cells, making them dependent on the functioning of proteins that repair damage to chromosomes. Therefore, drugs that target these proteins may be most effective against cells with a high level of loss of heterozygosity.

The authors also found that the profiles of loss of heterozygosity in low-grade serous ovarian cancer are similar to the profiles of heterozygosity of cells of triple-negative breast cancer, which are also characterized by a high level of chromosomal instability. This indicates a high probability of the existence of drugs that are effective against both diseases.

Article by Wang et al. Profiles of genomic instability in high-grade serous ovarian cancer predict treatment outcome is published in the journal Clinical Cancer Research.

Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of Dana-Farber Cancer Institute:
Researchers identify three subtypes of high-grade serous ovarian cancer.


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