New Findings on The Same Driver Gene Mutation Exists in All Metastatic Tumors from Individual Cancer

Most cancer-related deaths are caused by metastatic tumors, which are caused by the spread of primary tumors to distant parts of the body. Although primary tumors can usually be removed surgically, metastatic tumors often require treatment with standard chemotherapy or targeted therapy. The success of this novel targeted therapy depends on the presence of specific mutations in all cancer cells, particularly from metastatic tumors.

Prior to this, most studies aimed at targeting the genetic variability or heterogeneity of cancer have focused on primary tumors. While this information is still very valuable, however, much of the information is not known, such as cancer cells are notorious for their ability to change, evolve, and evade treatment, especially when they spread throughout the body.

Tumors consisting of billions of cells are full of genetic mutations; cancer cells and normal cells acquire many mutations when they divide, which makes the identification of driver mutations that significantly promote cancer production is critical for accurate oncology. In precision oncology, doctors aim to treat patients based on the genetic composition of their cancer.

In a new study, researchers from Stanford University School of Medicine, Harvard University, Memorial Sloan-Kettering Cancer Center, and Johns Hopkins University discovered a new finding in the way that cancers from individual patients spread or metastasize. Related results published in the Journal of Science.

Driven mutations occur in genes known to be involved in tumorigenesis, such as genes that normally control cell division. When a mutation occurs, these genes may promote cell division in an uncontrolled manner, thereby leading to cancer. Although hundreds of driver genes have been identified in different cancer types over the past few decades, relatively few mutations are thought to play an important role in cancer production in individual patients. Similarly, even in the driver genes, it is difficult to know which mutations are the real culprit (ie, driving mutations) or which mutations are ‘passenger mutations’.

In order to observe whether the driving gene mutations are identified in all metastatic tumors from individual cancer patients, the researchers analyzed DNA samples from 76 untreated metastatic tumors from 20 patients with 8 different cancer types, ensuring to obtain at least two different metastatic tumors from each patient.

Subsequently, the researchers selected mutations known to occur in the driving genes and investigated whether they were found in all metastatic tumors obtained from individual patients. In some cancers, they identified only two driving gene mutations, while in other cancers, they identified as many as 18 driver gene mutations.

By analyzing the data in this study in a large database containing more than 25,000 mutations of previously sequenced cancers, these researchers have found that driving gene mutations that are present in all metastatic tumors from individual patients are also frequently occurring in cancers that have previously been sequenced, which suggests that these mutations are true disease drivers and play a key role in cancer production.

These researchers also observed that a small number of driver gene mutations not found in all metastatic tumors from individual cancer patients are expected to produce weaker or no functional consequences. In other words, although these driver gene mutations occur in the driver gene, they are not present in all metastatic tumors, they may be passenger mutations, and may not play a key role in cancer production. This finding may open up new avenues for understanding tumor biopsy samples in the future.

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