Whole-exome sequencing identifies recurrent AKT1 mutations in sclerosing hemangioma of lung.
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.
Department of Microbiology, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea; Department of Integrated Research Center for Genome Polymorphism, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea;
Seung-Hyun
SH
Jung
Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea;
Min Sung
MS
Kim
Hospital Pathology, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea;
Sung-Hak
SH
Lee
Department of Microbiology, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea; Department of Integrated Research Center for Genome Polymorphism, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea;
Hyun-Chun
HC
Park
Hospital Pathology, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea;
Hyun Joo
HJ
Choi
Hospital Pathology, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea;
Leeso
L
Maeng
Hospital Pathology, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea;
Ki Ouk
KO
Min
Hospital Pathology, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea;
Jeana
J
Kim
Department of Pathology, Kyungpook National University School of Medicine, Daegu 41944, Korea;
Tae In
TI
Park
Hospital Pathology, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea;
Ok Ran
OR
Shin
Hospital Pathology, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea;
Tae-Jung
TJ
Kim
Center of Laboratory, Yanbian University Hospital, Yanji 133000, China;
Haidong
H
Xu
Hospital Pathology, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea;
Kyo Young
KY
Lee
Medical Informatics, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea;
Tae-Min
TM
Kim
Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Suwon 16419, Korea;
Sang Yong
SY
Song
The Jackson Laboratory for Genomic Medicine, Farmington, CT 06032; Department of Life Sciences, Ewha Woman's University, Seoul 03760, Korea.
Charles
C
Lee
Department of Microbiology, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea; Department of Integrated Research Center for Genome Polymorphism, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea; yejun@catholic.ac.kr suhulee@catholic.ac.kr.
Yeun-Jun
YJ
Chung
Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea; yejun@catholic.ac.kr suhulee@catholic.ac.kr.
Sug Hyung
SH
Lee
D000293:Adolescent; D000328:Adult; D000368:Aged; D059472:Exome / Q000235:genetics; D005260:Female; D015894:Genome, Human; D023281:Genomics; D018219:Histiocytoma, Benign Fibrous / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics*; D000073359:Exome Sequencing; D051176:beta Catenin / Q000235:genetics
D051176:beta Catenin; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt
AKT1 mutation; copy number alteration; pulmonary sclerosing hemangioma; whole-exome sequencing