| | | |

Exome Sequencing Helps Reveal Origins of Mesothelioma Tumor

22193632_genes2A type of genetic sequencing called whole exome sequencing (WES) may help scientists unlock the underlying causes of pleural mesothelioma and develop more targeted treatment plans.

A new study conducted in Italy and published in the journal Medicine illustrates how WES – the process of sequencing all of an individual’s protein-coding genes – helped reveal the origins of three different types of lung tumors in a patient with malignant pleural mesothelioma.

Mesothelioma Case Study

The study funded by the Italian Ministry of Health involved a 73-year-old man diagnosed with pleural mesothelioma, adenocarcinoma and squamous cell carcinoma.

The challenge was to determine whether the patient’s three tumors were somehow related or whether they arose independently. The answer could impact how doctors decided to treat them.

Using samples of cells from the mesothelioma tumor as well as the two lung cancer tumors, the team performed WES to determine each cancer’s genetic origin and the basis for the patient’s genetic cancer susceptibility.

In addition, a blood sample from the mesothelioma patient was used to perform WES of his germline DNA, the source of DNA for all other cells in the body.

Analyzing Individual Tumors

WES revealed that both of the lung cancers had a number of genetic mutations but that the list of mutations was different for each tumor. This suggested that the two tumors arose from separate tumor-specific “pathways”.

On the other hand, cells removed from the man’s pleural mesothelioma tumor had a relatively low number of genetic variants. One gene that was mutated was the WT1 gene, which, the researchers say, has been linked to non-asbestos-related mesothelioma.

Finally, WES analysis of the patient’s DNA showed problems with several genes responsible for making repairs when there is an error in DNA replication. These so-called “polymorphisms” in the DNA repair genes likely increased the man’s susceptibility to malignant mesothelioma and to lung cancer.

“Overall, WES did not disclose any somatic genetic variant shared across the 3 tumors, suggesting their clonal independency,” writes lead author Irene Vanni, MS, of the National Institute for Cancer Research in Genova.

Smoking Likely Played a Role in Mesothelioma

Although there was no single anomaly within the patient’s exome that could explain his mesothelioma and lung cancers, the researchers did point out that the man’s smoking habit probably played a role.

“The carcinogenic effect of smoke combined with a deficiency in DNA repair genes and the patient’s advanced age might have been responsible for the multiple primary tumor development,” the report concludes.

Genetic sequencing is playing an increasingly important role in healthcare, including cancer care. Understanding the genetic variants that may have given rise to a case of mesothelioma gives doctors the opportunity to develop highly-targeted new gene therapies.

Whole exome sequencing is far less expensive than complete genome sequencing because the exons make up only about one percent of the entire human genome.


Vanni, I, et al, “Whole exome sequencing of independent lung adenocarcinoma, lung squamous cell carcinoma, and malignant peritoneal mesothelioma: A case report”, November 2016, Medicine, e5447

Similar Posts