Seung-Hyun Junga,b, Min Sung Kimc, Sung-Hak Leed, Hyun-Chun Parka,b, Hyun Joo Choid, Leeso Maengd, Ki Ouk Mind, Jeana Kimd, Tae In Parke, Ok Ran Shind, Tae-Jung Kimd, Haidong Xuf, Kyo Young Leed, Tae-Min Kimg, Sang Yong Songh, Charles Leei,j, Yeun-Jun Chunga,b,1, and Sug Hyung Leec,1
aDepartment of Microbiology, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea;
bDepartment of Integrated Research Center for Genome Polymorphism, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea;
cDepartment of Pathology, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea;
dHospital Pathology, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea;
eDepartment of Pathology, Kyungpook National University School of Medicine, Daegu 41944, Korea;
fCenter of Laboratory, Yanbian University Hospital, Yanji 133000, China;
gMedical Informatics, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea;
hDepartment of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Suwon 16419, Korea;
iThe Jackson Laboratory for Genomic Medicine, Farmington, CT 06032;
jDepartment of Life Sciences, Ewha Woman’s University, Seoul 03760, Korea
Pulmonary sclerosing hemangioma (PSH) is a benign tumor with two cell populations (epithelial and stromal cells), for which genomic profiles remain unknown. We conducted exome sequencing of 44 PSHs and identified recurrent somatic mutations of AKT1 (43.2%) and β-catenin (4.5%). We used a second subset of 24 PSHs to confirm the high frequency of AKT1 mutations (overall 31/68, 45.6%; p.E17K, 33.8%) and recurrent β-catenin mutations (overall 3 of 68, 4.4%). Of the PSHs without AKT1 mutations, two exhibited AKT1 copy gain. AKT1 mutations existed in both epithelial and stromal cells. In two separate PSHs from one patient, we observed two different AKT1 mutations, indicating they were not disseminated but independent arising tumors. Because the AKT1 mutations were not found to co-occur with β-catenin mutations (or any other known driver alterations) in any of the PSHs studied, we speculate that this may be the single-most common driver alteration to develop PSHs. Our study revealed genomic differences between PSHs and lung adenocarcinomas, including a high rate of AKT1 mutation in PSHs. These genomic features of PSH identified in the present study provide clues to understanding the biology of PSH and for differential genomic diagnosis of lung tumors.
pulmonary sclerosing hemangioma, whole-exome sequencing, AKT1 mutation, copy number alteration
1To whom correspondence may be addressed.
Author contributions: Y.-J.C. and S.H.L. designed research; Y.-J.C. and S.H.L. performed research; S.-H.J., M.S.K., S.-H.L., H.-C.P., H.J.C., L.M., K.O.M., J.K., T.I.P., O.R.S., T.-J.K., H.X., K.Y.L., T.-M.K., and S.Y.S. analyzed data; and S.-H.J., C.L., Y.-J.C., and S.H.L. wrote the paper.