Clinical characteristics and genetic testing outcome of suspected hereditary peripheral nerve sheath tumours in a tertiary cancer institution in Singapore
Abstract Background Peripheral Nerve Sheath Tumors (PNST) are a diverse group of mostly benign tumours uncommon in the general population. About 5–10% of PNSTs are hereditary, predominantly arising from germline variants in NF1, NF2, SMARCB1, or LZTR1 gene. Methods We reviewed the clinical character...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-06-01
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| Series: | Hereditary Cancer in Clinical Practice |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13053-022-00230-4 |
| _version_ | 1811242193697898496 |
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| author | Jerold Loh Pei Yi Ong Denise Li Meng Goh Mark E. Puhaindran Balamurugan A. Vellayappan Samuel Guan Wei Ow Gloria Chan Soo-Chin Lee |
| author_facet | Jerold Loh Pei Yi Ong Denise Li Meng Goh Mark E. Puhaindran Balamurugan A. Vellayappan Samuel Guan Wei Ow Gloria Chan Soo-Chin Lee |
| author_sort | Jerold Loh |
| collection | DOAJ |
| description | Abstract Background Peripheral Nerve Sheath Tumors (PNST) are a diverse group of mostly benign tumours uncommon in the general population. About 5–10% of PNSTs are hereditary, predominantly arising from germline variants in NF1, NF2, SMARCB1, or LZTR1 gene. Methods We reviewed the clinical characteristics and genetic testing results of patients referred to the NCIS Adult Cancer Genetics Clinic for suspected hereditary PNST. Results 3,001 patients suspected to have various hereditary cancer syndromes were evaluated between year 2000 to March 2021. 13 (0.4%) were clinically diagnosed to have hereditary PNSTs. The majority were male (54%), with a median age at presentation to the genetics clinic of 29 years (range 19–48). 11/13 (85%) patients had multiple PNSTs, 12/13 (92%) had young onset PNSTs, 5/13 (38.5%) had personal and family history of PNST. 11/13 patients (85%) had clinical features of neurofibromatosis type 1 (NF1) including one patient who also fulfilled clinical criteria of neurofibromatosis type 2 (NF2); 2/13 (14%) had multiple schwannomas. Four patients underwent multi-gene panel testing, including one patient with clinical NF1, one patient who met both clinical NF1 and NF2 criteria, and two patients with multiple schwannomas. The patient with clinical features of NF1 was heterozygous for a pathogenic c. 2033dup variant in the NF1 gene. The patient with both NF1/NF2 features was heterozygous for a novel c.732 T > A nonsense variant in the NF2 gene. The two patients with multiple schwannomas were heterozygous for a pathogenic/likely pathogenic variant in the LZTR1 gene and are the first LZTR1-positive schwannomatosis patients reported in Asia. Conclusion Hereditary PNSTs are rare referrals to an adult cancer genetics clinic. NF1 is the most common PNST seen. LZTR1 variants may be the underlying cause in Asian patients with multiple schwannomatosis. |
| first_indexed | 2024-04-12T13:48:13Z |
| format | Article |
| id | doaj.art-23394bbd98f1439493664c22de883de6 |
| institution | Directory Open Access Journal |
| issn | 1897-4287 |
| language | English |
| last_indexed | 2024-04-12T13:48:13Z |
| publishDate | 2022-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Hereditary Cancer in Clinical Practice |
| spelling | doaj.art-23394bbd98f1439493664c22de883de62022-12-22T03:30:36ZengBMCHereditary Cancer in Clinical Practice1897-42872022-06-0120111110.1186/s13053-022-00230-4Clinical characteristics and genetic testing outcome of suspected hereditary peripheral nerve sheath tumours in a tertiary cancer institution in SingaporeJerold Loh0Pei Yi Ong1Denise Li Meng Goh2Mark E. Puhaindran3Balamurugan A. Vellayappan4Samuel Guan Wei Ow5Gloria Chan6Soo-Chin Lee7Department of Haematology-Oncology, NCIS, National University Cancer Institute, Singapore, National University Health SystemDepartment of Haematology-Oncology, NCIS, National University Cancer Institute, Singapore, National University Health SystemDivision of Paediatric Genetics and Metabolism, Department of Paediatrics, Khoo Teck Puat - National University Children’s Medical Institute, National University HospitalDepartment of Hand and Reconstructive Microsurgery, National University HospitalDepartment of Radiation Oncology, National University HospitalDepartment of Haematology-Oncology, NCIS, National University Cancer Institute, Singapore, National University Health SystemDepartment of Haematology-Oncology, NCIS, National University Cancer Institute, Singapore, National University Health SystemDepartment of Haematology-Oncology, NCIS, National University Cancer Institute, Singapore, National University Health SystemAbstract Background Peripheral Nerve Sheath Tumors (PNST) are a diverse group of mostly benign tumours uncommon in the general population. About 5–10% of PNSTs are hereditary, predominantly arising from germline variants in NF1, NF2, SMARCB1, or LZTR1 gene. Methods We reviewed the clinical characteristics and genetic testing results of patients referred to the NCIS Adult Cancer Genetics Clinic for suspected hereditary PNST. Results 3,001 patients suspected to have various hereditary cancer syndromes were evaluated between year 2000 to March 2021. 13 (0.4%) were clinically diagnosed to have hereditary PNSTs. The majority were male (54%), with a median age at presentation to the genetics clinic of 29 years (range 19–48). 11/13 (85%) patients had multiple PNSTs, 12/13 (92%) had young onset PNSTs, 5/13 (38.5%) had personal and family history of PNST. 11/13 patients (85%) had clinical features of neurofibromatosis type 1 (NF1) including one patient who also fulfilled clinical criteria of neurofibromatosis type 2 (NF2); 2/13 (14%) had multiple schwannomas. Four patients underwent multi-gene panel testing, including one patient with clinical NF1, one patient who met both clinical NF1 and NF2 criteria, and two patients with multiple schwannomas. The patient with clinical features of NF1 was heterozygous for a pathogenic c. 2033dup variant in the NF1 gene. The patient with both NF1/NF2 features was heterozygous for a novel c.732 T > A nonsense variant in the NF2 gene. The two patients with multiple schwannomas were heterozygous for a pathogenic/likely pathogenic variant in the LZTR1 gene and are the first LZTR1-positive schwannomatosis patients reported in Asia. Conclusion Hereditary PNSTs are rare referrals to an adult cancer genetics clinic. NF1 is the most common PNST seen. LZTR1 variants may be the underlying cause in Asian patients with multiple schwannomatosis.https://doi.org/10.1186/s13053-022-00230-4Peripheral nerve sheath tumorsSchwannomatosisNeurofibromatosisLZTR1 variantsGenetics |
| spellingShingle | Jerold Loh Pei Yi Ong Denise Li Meng Goh Mark E. Puhaindran Balamurugan A. Vellayappan Samuel Guan Wei Ow Gloria Chan Soo-Chin Lee Clinical characteristics and genetic testing outcome of suspected hereditary peripheral nerve sheath tumours in a tertiary cancer institution in Singapore Hereditary Cancer in Clinical Practice Peripheral nerve sheath tumors Schwannomatosis Neurofibromatosis LZTR1 variants Genetics |
| title | Clinical characteristics and genetic testing outcome of suspected hereditary peripheral nerve sheath tumours in a tertiary cancer institution in Singapore |
| title_full | Clinical characteristics and genetic testing outcome of suspected hereditary peripheral nerve sheath tumours in a tertiary cancer institution in Singapore |
| title_fullStr | Clinical characteristics and genetic testing outcome of suspected hereditary peripheral nerve sheath tumours in a tertiary cancer institution in Singapore |
| title_full_unstemmed | Clinical characteristics and genetic testing outcome of suspected hereditary peripheral nerve sheath tumours in a tertiary cancer institution in Singapore |
| title_short | Clinical characteristics and genetic testing outcome of suspected hereditary peripheral nerve sheath tumours in a tertiary cancer institution in Singapore |
| title_sort | clinical characteristics and genetic testing outcome of suspected hereditary peripheral nerve sheath tumours in a tertiary cancer institution in singapore |
| topic | Peripheral nerve sheath tumors Schwannomatosis Neurofibromatosis LZTR1 variants Genetics |
| url | https://doi.org/10.1186/s13053-022-00230-4 |
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