Scientists have discovered the source of cancer and have new ideas for treating cancer

In the development of cancer biology in the past decades, people have reached a consensus on the origin of cancer, that is, during the process of normal cell division, gene mutations continue to accumulate, leading to the activation of oncogenes and the inactivation of tumor suppressor genes

 But in fact, in every normal person's body, there may be thousands of DNA mutant cells, but only in rare cases, these DNA mutant cells will become cancerous, leading to the occurrence of cancer

But why? 

The traditional explanation is that cancer only occurs when the number of cells with DNA mutations reaches a certain threshold

Now, the latest research by researchers at Memorial Sloan Kettering Cancer Research Center (MSK) has successfully subverted this traditional view

A research team led by Richard M.

They confirmed in the zebrafish melanoma susceptibility model that knocking out the ATAD2 gene, even if there are many carcinogenic and tumor suppressor gene mutations, the cells still cannot become cancerous, and adding the ATAD2 gene restores the ability of the cells to become cancerous

Therefore, researchers believe that although genetic mutations are a key driver of cancer formation, not all cells that undergo mutations will become cancerous

The lead author of the study, Dr.

The relevant research results were published in the latest issue of "Science" with the title "Developmental Chromatin Program Determines the Carcinogenicity of Melanoma"

Why can't melanocytic nevi become cancerous? 

In recent years, through advanced technologies such as genome hybridization and sequencing, scientists have discovered a series of key cell signaling pathways and related genes

In 2003, shortly after the BRAF carcinogenic mutation was discovered, Professor Pollock and others discovered the same mutation in melanocytic nevi with a mutation rate as high as 82%

Around 2010, during his postdoctoral research, Professor White found that in the zebrafish melanoma model, the genetic characteristics of many cancer cells are more inclined to embryonic cells than mature melanocytes

Later, during the genetic modification of the zebrafish melanoma model, Professor White further discovered that the introduction of the BRAF gene at different stages of melanocyte development would lead to different results

In order to further confirm that this phenomenon also exists in humans, Professor White and Dr.

Therefore, Professor White and Dr.

These results indicate that gene mutation alone is not enough to make normal cells cancerous

Who gave the cells the ability to become cancerous? 

In fact, Professor White is not the first person interested in this phenomenon
.

In 2016, Professor Leonard Zon of Boston Children's Hospital discovered that some cells in the human body have already developed cancer-causing mutations, but they are not cancerous cells
.
Later, it was demonstrated in a zebrafish melanoma model that even if all zebrafish carry the BRAF mutation and lose the tumor suppressor gene p53, tumors will only form when the Crestin gene is activated
.
Related research is also published in the journal "Science"
.

At the same time, Professor Zon proposed a new model of cancer formation
.
When oncogenes are activated and anti-oncogenes are silenced or lost, normal tissue is ready to become cancerous, but only one cell in the tissue returns to a more primitive embryonic state and begins to divide
.
Cancer will only form within a period of time
.
They believe that this model is not only suitable for melanoma, but also for most (not all) cancers
.
 

In this study, Professor White and Dr.
Studer conducted a systematic analysis of the gene expression of zebrafish and hspc-derived neural crest stage, melanocyte stage and mature melanocytes, aiming to find the differences between the three
.
In the end, they found that the biggest difference between the three is a specific gene ATAD2, which is active in the neural crest stage and the melanocyte stage, but not active in mature melanocytes
.

ATAD2 is called a chromatin modifier, which can bind to the gene region near the chromosome and activate genes related to embryonic development through epigenetic modification
.
In recent years, a large number of studies have shown that ATAD2 is a typical cancer-related molecule that plays an important role in the occurrence and development of prostate cancer, breast cancer, melanoma and other cancers
.

To prove that ATAD2 plays a decisive role in the formation of melanoma, the researchers removed the melanoma zebrafish model and then added the ATAD2 gene again
.
Studies have found that when the ATAD2 gene is removed, the cell loses the ability to become cancerous, and when ATAD2 is added to the cell again, the cell can restore this ability
.
This means that the ATAD2 gene is the key to the smooth formation of melanoma
.

The role of ATAD2 in the process of cell carcinogenesis (Source: Science)

Finally, using a large amount of data provided by MSK and Cancer Genome Atlas, researchers found that the survival rate of cancer patients activated by the ATAD2 gene was significantly reduced, which means that it plays an important role in the cancer genome
.

In general, the latest research by Professor White, Dr.
Studder and their team shows that the formation of melanoma depends on the "carcinogenic ability" of the ATAD2 gene
.
Without it, even if there are many cancer-causing mutations, melanocytes will not become cancerous
.
 

Researchers say their findings provide an important new perspective for the formation of cancer, which is in sharp contrast with traditional views
.
 

"The standard view that has existed for decades is that cancer basically requires two types of DNA mutations: activated oncogenes and missing tumor suppressor genes
.
Once these two barriers are cleared, cancer will develop
.
Now we have Something completely different-carcinogenicity-adds a third dimension to the occurrence of cancer
.
"

The more important significance of this research result is that in the future, targeting the ATAD2 gene may open up a new way for tumor treatment
.
The hPSC technology developed by the melanoma team may also prove to be widely used in personalized cancer treatment
.