Распространение раковых клеток определено с помощью новой модели, разработанной в YSPH

Исследователи из Йельской школы общественного здравоохранения обнаружили математическую зависимость, которая проливает свет на скорости, при которой раковые клетки мутируют и почему некоторые выживают и быстро размножаются, пока другие не делают.

Фото кредит: Istock

Открытие членами лаборатории Джеффри Таунсенд, Доктор философии, Elihu профессор биостатистики и экология и эволюционная биология, will allow essential calculations to be performed that determine the likely scope of cancerous cells as they develop.

The finding has implications for decision-making for precision-medicine tumor boards, the selection and design of clinical trials, the development of pharmaceuticals and basic research prioritization.

The study is published in the Journal of the National Cancer Institute.

“For the past 10 лет мы были в состоянии вычислить из опухоли последовательности, которые мутантного гена являются победителями и проигравшими-которые мутировали гены помогают рак выживать и размножаться, и которые ничего не делают,»Сказал Таунсенд. «Но мы не смогли вычислить их размерный эффект рака-как важная мутация по сравнению с другим. Теперь мы можем «.

A major goal of cancer biology is to not just identify the important and unimportant genes to the development of cancer, but to determine the relative importance of each cellular mutation to the survival and spread of cancer cells and, в конечном счете, what it means for the patient, Townsend explained.

В исследовании, the researchers estimated the effect sizes of all recurrent single nucleotide variants in 22 major types of cancer, and quantified the relative importance of each.

Tumor sequencing studies have typically reported how frequent mutations are seen and a statistical measure (a п ценить) indicating whether the gene is overburdened with mutations beyond expectation, both important measures. тем не мение, neither measure is an effect size for cancer. Neither measure communicates how important the gene is to tumorigenesis and cancer disease. To quantify cancer effect size, Townsend and colleagues broke down the frequency that a mutation is observed in tumors into two contributing factors: the baseline mutation rate, and the degree of selection for the mutation in the cancer lineage. Both mutation and selection contribute to the frequency of variants among cells. Townsend and colleagues were able to use diverse genome-scale data to calculate the mutation rate. By essentially dividing out the contribution of mutation from the frequency that mutations were observed in tumors, they showed how to calculate the cancer effect size

Townsend credits the breakthrough to insights that come from having a background in evolutionary biology. “Whereas in the cancer world the focus has always been on mutation rates, the focus in evolutionary biology has been on the process of natural selection on those mutations. The quantification of cancer effect sizes is a great example of how interdisciplinary research is not only helpful, but essential to scientific progress," он сказал.

Why is the cancer effect size important? Townsend uses an example of a tumor, from which a DNA sequence shows that two genes known to be related to cancer have mutated. There are two highly effective drugs targeting these exact mutations but no clinical trial has been conducted to compare them.

“By looking at cancer through the lens of evolution we can harness the wealth of molecular data made available through tumor DNA sequencing to both better understand what is driving cancer and to also expand and refine evolutionary theory,” said Vincent Cannataro, Доктор философии, a postdoctoral associate and the study’s first author.

The study was co-authored by Stephen Gaffney, Доктор философии, an associate research scientist at the Yale School of Public Health. The research was funded by a grant from Gilead Sciences, Inc.

Источник: publichealth.yale.edu, by Elisabeth Reitman