Mutation Profile of Aggressive Pheochromocytoma and Paraganglioma with Comparison of TCGA Data
In pheochromocytoma and paraganglioma (PPGL), germline or somatic mutations in one of the known susceptibility genes are identified in up to 60% patients. However, the peculiar genetic events that drive the aggressive behavior including metastasis in PPGL are poorly understood. We performed targeted...
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MDPI AG
2021-05-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/10/2389 |
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| author | Yun Mi Choi Jinyeong Lim Min Ji Jeon Yu-Mi Lee Tae-Yon Sung Eun-Gyoung Hong Ji-Young Lee Se Jin Jang Won Gu Kim Dong Eun Song Sung-Min Chun |
| author_facet | Yun Mi Choi Jinyeong Lim Min Ji Jeon Yu-Mi Lee Tae-Yon Sung Eun-Gyoung Hong Ji-Young Lee Se Jin Jang Won Gu Kim Dong Eun Song Sung-Min Chun |
| author_sort | Yun Mi Choi |
| collection | DOAJ |
| description | In pheochromocytoma and paraganglioma (PPGL), germline or somatic mutations in one of the known susceptibility genes are identified in up to 60% patients. However, the peculiar genetic events that drive the aggressive behavior including metastasis in PPGL are poorly understood. We performed targeted next-generation sequencing analysis to characterize the mutation profile in fifteen aggressive PPGL patients and compared accessible data of aggressive PPGLs from The Cancer Genome Atlas (TCGA) with findings of our cohort. A total of 115 germline and 34 somatic variants were identified with a median 0.58 per megabase tumor mutation burden in our cohort. The most frequent mutation was <i>SDHB</i> germline mutation (27%) and the second frequent mutations were somatic mutations for <i>SETD2</i>, <i>NF1</i>, and <i>HRAS</i> (13%, respectively). Patients were subtyped into three categories based on the kind of mutated genes: pseudohypoxia (<i>n</i> = 5), kinase (<i>n</i> = 5), and unknown (<i>n</i> = 5) group. In copy number variation analysis, deletion of chromosome arm 1p harboring <i>SDHB</i> gene was the most frequently observed. In our cohort, <i>SDHB</i> mutation and pseudohypoxia subtype were significantly associated with poor overall survival. In conclusion, subtyping of mutation profile can be helpful in aggressive PPGL patients with heterogeneous prognosis to make relevant follow-up plan and achieve proper treatment. |
| first_indexed | 2024-03-10T11:24:15Z |
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| language | English |
| last_indexed | 2024-03-10T11:24:15Z |
| publishDate | 2021-05-01 |
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| record_format | Article |
| series | Cancers |
| spelling | doaj.art-b9699b2f1ccc410797a79de9301f4c502023-11-21T19:49:48ZengMDPI AGCancers2072-66942021-05-011310238910.3390/cancers13102389Mutation Profile of Aggressive Pheochromocytoma and Paraganglioma with Comparison of TCGA DataYun Mi Choi0Jinyeong Lim1Min Ji Jeon2Yu-Mi Lee3Tae-Yon Sung4Eun-Gyoung Hong5Ji-Young Lee6Se Jin Jang7Won Gu Kim8Dong Eun Song9Sung-Min Chun10Department of Internal Medicine, Hallym University Dongtan Sacred Heart Hospital, Hallym University College of Medicine, Gyeonggi-Do 18450, KoreaAsan Center for Cancer Genome Discovery, Asan Institute for Life Sciences, Seoul 05505, KoreaDepartment of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, KoreaDepartment of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, KoreaDepartment of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, KoreaDepartment of Internal Medicine, Hallym University Dongtan Sacred Heart Hospital, Hallym University College of Medicine, Gyeonggi-Do 18450, KoreaDepartment of Medical Science, Asan Medical Center, Asan Medical Institute of Convergence Science and Technology, University of Ulsan College of Medicine, Seoul 05505, KoreaAsan Center for Cancer Genome Discovery, Asan Institute for Life Sciences, Seoul 05505, KoreaDepartment of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, KoreaDepartment of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, KoreaAsan Center for Cancer Genome Discovery, Asan Institute for Life Sciences, Seoul 05505, KoreaIn pheochromocytoma and paraganglioma (PPGL), germline or somatic mutations in one of the known susceptibility genes are identified in up to 60% patients. However, the peculiar genetic events that drive the aggressive behavior including metastasis in PPGL are poorly understood. We performed targeted next-generation sequencing analysis to characterize the mutation profile in fifteen aggressive PPGL patients and compared accessible data of aggressive PPGLs from The Cancer Genome Atlas (TCGA) with findings of our cohort. A total of 115 germline and 34 somatic variants were identified with a median 0.58 per megabase tumor mutation burden in our cohort. The most frequent mutation was <i>SDHB</i> germline mutation (27%) and the second frequent mutations were somatic mutations for <i>SETD2</i>, <i>NF1</i>, and <i>HRAS</i> (13%, respectively). Patients were subtyped into three categories based on the kind of mutated genes: pseudohypoxia (<i>n</i> = 5), kinase (<i>n</i> = 5), and unknown (<i>n</i> = 5) group. In copy number variation analysis, deletion of chromosome arm 1p harboring <i>SDHB</i> gene was the most frequently observed. In our cohort, <i>SDHB</i> mutation and pseudohypoxia subtype were significantly associated with poor overall survival. In conclusion, subtyping of mutation profile can be helpful in aggressive PPGL patients with heterogeneous prognosis to make relevant follow-up plan and achieve proper treatment.https://www.mdpi.com/2072-6694/13/10/2389aggressive pheochromocytomaparagangliomaDNA mutation analysishigh-throughput nucleotide sequencingprognosis |
| spellingShingle | Yun Mi Choi Jinyeong Lim Min Ji Jeon Yu-Mi Lee Tae-Yon Sung Eun-Gyoung Hong Ji-Young Lee Se Jin Jang Won Gu Kim Dong Eun Song Sung-Min Chun Mutation Profile of Aggressive Pheochromocytoma and Paraganglioma with Comparison of TCGA Data Cancers aggressive pheochromocytoma paraganglioma DNA mutation analysis high-throughput nucleotide sequencing prognosis |
| title | Mutation Profile of Aggressive Pheochromocytoma and Paraganglioma with Comparison of TCGA Data |
| title_full | Mutation Profile of Aggressive Pheochromocytoma and Paraganglioma with Comparison of TCGA Data |
| title_fullStr | Mutation Profile of Aggressive Pheochromocytoma and Paraganglioma with Comparison of TCGA Data |
| title_full_unstemmed | Mutation Profile of Aggressive Pheochromocytoma and Paraganglioma with Comparison of TCGA Data |
| title_short | Mutation Profile of Aggressive Pheochromocytoma and Paraganglioma with Comparison of TCGA Data |
| title_sort | mutation profile of aggressive pheochromocytoma and paraganglioma with comparison of tcga data |
| topic | aggressive pheochromocytoma paraganglioma DNA mutation analysis high-throughput nucleotide sequencing prognosis |
| url | https://www.mdpi.com/2072-6694/13/10/2389 |
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