Research Highlight September 06, 2016

Benign lung tumors found to have a high rate of mutation in a single gene

A form of benign lung tumor known as pulmonary sclerosing hemangioma (PSH) has been shown to share its origin with malignant lung adenocarcinoma. The genetic mechanisms underlying their differing tumor development had not previously been investigated. However, a research team led by Sug Hyung Lee of The Catholic University of Korea and including JAX Genomic Medicine Scientific Director Charles Lee, Ph.D., FACMG (who is also a Professor at Ewha Womans University in Korea), investigated the genetic alterations in PSH tumors using whole exome sequencing (WES). The results, published in “Whole-exome sequencing identifies recurrent AKT1 mutations in sclerosing hemangioma of lung” in The Proceedings of the National Academy of Sciences, found mutations in multiple genes, but in only one at high frequency.

The gene, AKT1, is one of three closely related serine/threonine-protein kinases (AKT1, AKT2 and AKT3). It regulates many cancer-related cellular processes, including proliferation, growth and survival. Overall, the researchers found AKT1 mutations in 31/68 (45.6%) of tumors sequenced. While mutations were distributed at different sites within the AKT1 gene, 23 were p.E17K, a specific AKT1 mutation that has also been found in breast cancers but rarely in lung cancers. Copy number alterations (CNAs) were also found in 15.9% of tumors analyzed, far fewer than that found in malignant lung cancers.

The data suggest that AKT1 gene alterations may be the most common driver of PSH development. Another gene, β-catenin, was also found to have recurrent mutations, although in only 3/68 (4.4%) of the tumors. The two mutations were not found to co-occur, however, a finding in contrast with adenocarcinomas, which contain multiple driver mutations. It’s possible that these mutations alone may be enough to produce a benign tumor but not enough to drive malignant tumor growth. The different mutation load also provides the basis for differential genomic diagnosis of lung tumors.


www.pnas.org/cgi/doi/10.1073/pnas.1606946113