YAP1 Germline Mutation Increases Risk for Lung Adenocarcinoma

YAP1 Germline Mutation Increases Risk for Lung Adenocarcinoma

June 22, 2015

The cause of lung cancer in nonsmokers has not always been clear, but a new study published in the Journal of Clinical Oncology reported that a specific germline mutation, called YAP1, puts carriers at a higher risk when compared to the general population.

The cause of lung cancer in nonsmokers has not always been clear, but a new study published in the Journal of Clinical Oncology reported that a specific germline mutation, called YAP1, puts carriers at a higher risk when compared to the general population.1

Prior to this finding, only two germline mutations, T790M and V843I (both epidermal growth factor receptor mutations), had been identified as being a potential cause of cases of familial lung adenocarcinoma.

Researchers at the Taichung Veterans General Hospital in Taiwan performed whole-genome sequencing on a family who experienced a high-level of lung adenocarcinoma.

Hsuan-Yu Chen, M. S., and colleagues procured DNA from an affected mother, four affected daughters, and one nonaffected son to look at the role of hereditary factors that contributed to this disease. The researchers then validated their findings against an external cohort of 1,135 participants without cancer and 1,312 patients with lung adenocarcinoma. Participants for this study were drawn from the Genetic Epidemiology Study of Lung Adenocarcinoma (GELAC) and the Cancer Screening Project (CSP).

The researchers performed follow-up procedures such as genotyping the relatives of the original proband and the relatives of the identified risk-allele carriers. Low-dose computed tomography (CT) scans of the chest were evaluated for lung abnormalities.

The results showed that the YAP1 R331W oncogene is an allele that predisposes carriers to lung adenocarcinoma, along with their family members.  Because of this, researchers recommend low-dose CT scans too for this subpopulation, which is also at high-risk for lung cancer.

The mechanism through which the YAP1 R331W germline mutation confers predisposition to lung cancer is unclear. This mutation can bind to many transcription factors and modulate activities of the transcription factors to promote cell growth and inhibit apoptosis.

Additional studies into how this mechanism works in cancer development will be helpful to further the understanding of causation and perhaps lead to prevention strategies.

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