Profiling PIK3CA variants in disorders of somatic mosaicism
Purpose: Variants in PIK3CA (encoding p110α; the catalytic subunit of PI3K) characterize some disorders of somatic mosaicism (DoSM) conditions with clinical features, including sporadic overgrowth and vascular malformations. Here, we profile PIK3CA variants in DoSM. Methods: We applied a next-genera...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Bahareh A. Mojarad [verfasserIn] Patricia V. Hernandez [verfasserIn] Michael J. Evenson [verfasserIn] Meagan M. Corliss [verfasserIn] Sarah L. Stein [verfasserIn] Amy Theos [verfasserIn] Carrie C. Coughlin [verfasserIn] Bryan Sisk [verfasserIn] Maithilee Menezes [verfasserIn] Molly C. Schroeder [verfasserIn] Jonathan W. Heusel [verfasserIn] Julie A. Neidich [verfasserIn] Yang Cao [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2023 |
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| Schlagwörter: |
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| Übergeordnetes Werk: |
In: Genetics in Medicine Open ; 1(2023), 1, Seite 100815- volume:1 ; year:2023 ; number:1 ; pages:100815- |
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| Links: |
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| DOI / URN: |
10.1016/j.gimo.2023.100815 |
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| Katalog-ID: |
DOAJ096272465 |
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| 520 | |a Purpose: Variants in PIK3CA (encoding p110α; the catalytic subunit of PI3K) characterize some disorders of somatic mosaicism (DoSM) conditions with clinical features, including sporadic overgrowth and vascular malformations. Here, we profile PIK3CA variants in DoSM. Methods: We applied a next-generation, sequencing-based, laboratory-developed test, using an average coverage of approximately 2000× for up to 37 genes associated with DoSM, on a cohort of 1197 patients with DoSM referred for clinical genomics services between 2013 and 2022. Results: We identified clinically reportable variants in 747 (62.4%) individuals in this cohort. Notably, 371 clinically reportable variants in PIK3CA were identified in 368 patients, constituting approximately 49.2% of all patients with reportable findings. Variants in the C2 domain of p110α are enriched in DoSM (this cohort) compared with those of cancer (Catalogue of Somatic Mutations in Cancer [COSMIC] database), highlighting the role of the C2 domain in driving uncontrolled cell proliferation in DoSM. Furthermore, we report 17 novel variants in PIK3CA that are not previously reported in DoSM and describe clinical presentation correlation for 4 novel variants. Conclusion: Our findings from the largest single-center cohort of patients with DoSM expand the spectrum of variants in PIK3CA and shed light on the less-studied role of the C2 domain in the pathogenesis of DoSM. | ||
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10.1016/j.gimo.2023.100815 doi (DE-627)DOAJ096272465 (DE-599)DOAJ8ea711a209f14e6298e7a8cde88994e4 DE-627 ger DE-627 rakwb eng QH426-470 Bahareh A. Mojarad verfasserin aut Profiling PIK3CA variants in disorders of somatic mosaicism 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Purpose: Variants in PIK3CA (encoding p110α; the catalytic subunit of PI3K) characterize some disorders of somatic mosaicism (DoSM) conditions with clinical features, including sporadic overgrowth and vascular malformations. Here, we profile PIK3CA variants in DoSM. Methods: We applied a next-generation, sequencing-based, laboratory-developed test, using an average coverage of approximately 2000× for up to 37 genes associated with DoSM, on a cohort of 1197 patients with DoSM referred for clinical genomics services between 2013 and 2022. Results: We identified clinically reportable variants in 747 (62.4%) individuals in this cohort. Notably, 371 clinically reportable variants in PIK3CA were identified in 368 patients, constituting approximately 49.2% of all patients with reportable findings. Variants in the C2 domain of p110α are enriched in DoSM (this cohort) compared with those of cancer (Catalogue of Somatic Mutations in Cancer [COSMIC] database), highlighting the role of the C2 domain in driving uncontrolled cell proliferation in DoSM. Furthermore, we report 17 novel variants in PIK3CA that are not previously reported in DoSM and describe clinical presentation correlation for 4 novel variants. Conclusion: Our findings from the largest single-center cohort of patients with DoSM expand the spectrum of variants in PIK3CA and shed light on the less-studied role of the C2 domain in the pathogenesis of DoSM. NGS PIK3CA PIK3CA-related overgrowth spectrum PROS Somatic mosaicism Genetics Medicine R Patricia V. Hernandez verfasserin aut Michael J. Evenson verfasserin aut Meagan M. Corliss verfasserin aut Sarah L. Stein verfasserin aut Amy Theos verfasserin aut Carrie C. Coughlin verfasserin aut Bryan Sisk verfasserin aut Maithilee Menezes verfasserin aut Molly C. Schroeder verfasserin aut Jonathan W. Heusel verfasserin aut Julie A. Neidich verfasserin aut Yang Cao verfasserin aut In Genetics in Medicine Open 1(2023), 1, Seite 100815- volume:1 year:2023 number:1 pages:100815- https://doi.org/10.1016/j.gimo.2023.100815 kostenfrei https://doaj.org/article/8ea711a209f14e6298e7a8cde88994e4 kostenfrei http://www.sciencedirect.com/science/article/pii/S2949774423008245 kostenfrei https://doaj.org/toc/2949-7744 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ AR 1 2023 1 100815- |
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10.1016/j.gimo.2023.100815 doi (DE-627)DOAJ096272465 (DE-599)DOAJ8ea711a209f14e6298e7a8cde88994e4 DE-627 ger DE-627 rakwb eng QH426-470 Bahareh A. Mojarad verfasserin aut Profiling PIK3CA variants in disorders of somatic mosaicism 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Purpose: Variants in PIK3CA (encoding p110α; the catalytic subunit of PI3K) characterize some disorders of somatic mosaicism (DoSM) conditions with clinical features, including sporadic overgrowth and vascular malformations. Here, we profile PIK3CA variants in DoSM. Methods: We applied a next-generation, sequencing-based, laboratory-developed test, using an average coverage of approximately 2000× for up to 37 genes associated with DoSM, on a cohort of 1197 patients with DoSM referred for clinical genomics services between 2013 and 2022. Results: We identified clinically reportable variants in 747 (62.4%) individuals in this cohort. Notably, 371 clinically reportable variants in PIK3CA were identified in 368 patients, constituting approximately 49.2% of all patients with reportable findings. Variants in the C2 domain of p110α are enriched in DoSM (this cohort) compared with those of cancer (Catalogue of Somatic Mutations in Cancer [COSMIC] database), highlighting the role of the C2 domain in driving uncontrolled cell proliferation in DoSM. Furthermore, we report 17 novel variants in PIK3CA that are not previously reported in DoSM and describe clinical presentation correlation for 4 novel variants. Conclusion: Our findings from the largest single-center cohort of patients with DoSM expand the spectrum of variants in PIK3CA and shed light on the less-studied role of the C2 domain in the pathogenesis of DoSM. NGS PIK3CA PIK3CA-related overgrowth spectrum PROS Somatic mosaicism Genetics Medicine R Patricia V. Hernandez verfasserin aut Michael J. Evenson verfasserin aut Meagan M. Corliss verfasserin aut Sarah L. Stein verfasserin aut Amy Theos verfasserin aut Carrie C. Coughlin verfasserin aut Bryan Sisk verfasserin aut Maithilee Menezes verfasserin aut Molly C. Schroeder verfasserin aut Jonathan W. Heusel verfasserin aut Julie A. Neidich verfasserin aut Yang Cao verfasserin aut In Genetics in Medicine Open 1(2023), 1, Seite 100815- volume:1 year:2023 number:1 pages:100815- https://doi.org/10.1016/j.gimo.2023.100815 kostenfrei https://doaj.org/article/8ea711a209f14e6298e7a8cde88994e4 kostenfrei http://www.sciencedirect.com/science/article/pii/S2949774423008245 kostenfrei https://doaj.org/toc/2949-7744 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ AR 1 2023 1 100815- |
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10.1016/j.gimo.2023.100815 doi (DE-627)DOAJ096272465 (DE-599)DOAJ8ea711a209f14e6298e7a8cde88994e4 DE-627 ger DE-627 rakwb eng QH426-470 Bahareh A. Mojarad verfasserin aut Profiling PIK3CA variants in disorders of somatic mosaicism 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Purpose: Variants in PIK3CA (encoding p110α; the catalytic subunit of PI3K) characterize some disorders of somatic mosaicism (DoSM) conditions with clinical features, including sporadic overgrowth and vascular malformations. Here, we profile PIK3CA variants in DoSM. Methods: We applied a next-generation, sequencing-based, laboratory-developed test, using an average coverage of approximately 2000× for up to 37 genes associated with DoSM, on a cohort of 1197 patients with DoSM referred for clinical genomics services between 2013 and 2022. Results: We identified clinically reportable variants in 747 (62.4%) individuals in this cohort. Notably, 371 clinically reportable variants in PIK3CA were identified in 368 patients, constituting approximately 49.2% of all patients with reportable findings. Variants in the C2 domain of p110α are enriched in DoSM (this cohort) compared with those of cancer (Catalogue of Somatic Mutations in Cancer [COSMIC] database), highlighting the role of the C2 domain in driving uncontrolled cell proliferation in DoSM. Furthermore, we report 17 novel variants in PIK3CA that are not previously reported in DoSM and describe clinical presentation correlation for 4 novel variants. Conclusion: Our findings from the largest single-center cohort of patients with DoSM expand the spectrum of variants in PIK3CA and shed light on the less-studied role of the C2 domain in the pathogenesis of DoSM. NGS PIK3CA PIK3CA-related overgrowth spectrum PROS Somatic mosaicism Genetics Medicine R Patricia V. Hernandez verfasserin aut Michael J. Evenson verfasserin aut Meagan M. Corliss verfasserin aut Sarah L. Stein verfasserin aut Amy Theos verfasserin aut Carrie C. Coughlin verfasserin aut Bryan Sisk verfasserin aut Maithilee Menezes verfasserin aut Molly C. Schroeder verfasserin aut Jonathan W. Heusel verfasserin aut Julie A. Neidich verfasserin aut Yang Cao verfasserin aut In Genetics in Medicine Open 1(2023), 1, Seite 100815- volume:1 year:2023 number:1 pages:100815- https://doi.org/10.1016/j.gimo.2023.100815 kostenfrei https://doaj.org/article/8ea711a209f14e6298e7a8cde88994e4 kostenfrei http://www.sciencedirect.com/science/article/pii/S2949774423008245 kostenfrei https://doaj.org/toc/2949-7744 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ AR 1 2023 1 100815- |
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10.1016/j.gimo.2023.100815 doi (DE-627)DOAJ096272465 (DE-599)DOAJ8ea711a209f14e6298e7a8cde88994e4 DE-627 ger DE-627 rakwb eng QH426-470 Bahareh A. Mojarad verfasserin aut Profiling PIK3CA variants in disorders of somatic mosaicism 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Purpose: Variants in PIK3CA (encoding p110α; the catalytic subunit of PI3K) characterize some disorders of somatic mosaicism (DoSM) conditions with clinical features, including sporadic overgrowth and vascular malformations. Here, we profile PIK3CA variants in DoSM. Methods: We applied a next-generation, sequencing-based, laboratory-developed test, using an average coverage of approximately 2000× for up to 37 genes associated with DoSM, on a cohort of 1197 patients with DoSM referred for clinical genomics services between 2013 and 2022. Results: We identified clinically reportable variants in 747 (62.4%) individuals in this cohort. Notably, 371 clinically reportable variants in PIK3CA were identified in 368 patients, constituting approximately 49.2% of all patients with reportable findings. Variants in the C2 domain of p110α are enriched in DoSM (this cohort) compared with those of cancer (Catalogue of Somatic Mutations in Cancer [COSMIC] database), highlighting the role of the C2 domain in driving uncontrolled cell proliferation in DoSM. Furthermore, we report 17 novel variants in PIK3CA that are not previously reported in DoSM and describe clinical presentation correlation for 4 novel variants. Conclusion: Our findings from the largest single-center cohort of patients with DoSM expand the spectrum of variants in PIK3CA and shed light on the less-studied role of the C2 domain in the pathogenesis of DoSM. NGS PIK3CA PIK3CA-related overgrowth spectrum PROS Somatic mosaicism Genetics Medicine R Patricia V. Hernandez verfasserin aut Michael J. Evenson verfasserin aut Meagan M. Corliss verfasserin aut Sarah L. Stein verfasserin aut Amy Theos verfasserin aut Carrie C. Coughlin verfasserin aut Bryan Sisk verfasserin aut Maithilee Menezes verfasserin aut Molly C. Schroeder verfasserin aut Jonathan W. Heusel verfasserin aut Julie A. Neidich verfasserin aut Yang Cao verfasserin aut In Genetics in Medicine Open 1(2023), 1, Seite 100815- volume:1 year:2023 number:1 pages:100815- https://doi.org/10.1016/j.gimo.2023.100815 kostenfrei https://doaj.org/article/8ea711a209f14e6298e7a8cde88994e4 kostenfrei http://www.sciencedirect.com/science/article/pii/S2949774423008245 kostenfrei https://doaj.org/toc/2949-7744 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ AR 1 2023 1 100815- |
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10.1016/j.gimo.2023.100815 doi (DE-627)DOAJ096272465 (DE-599)DOAJ8ea711a209f14e6298e7a8cde88994e4 DE-627 ger DE-627 rakwb eng QH426-470 Bahareh A. Mojarad verfasserin aut Profiling PIK3CA variants in disorders of somatic mosaicism 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Purpose: Variants in PIK3CA (encoding p110α; the catalytic subunit of PI3K) characterize some disorders of somatic mosaicism (DoSM) conditions with clinical features, including sporadic overgrowth and vascular malformations. Here, we profile PIK3CA variants in DoSM. Methods: We applied a next-generation, sequencing-based, laboratory-developed test, using an average coverage of approximately 2000× for up to 37 genes associated with DoSM, on a cohort of 1197 patients with DoSM referred for clinical genomics services between 2013 and 2022. Results: We identified clinically reportable variants in 747 (62.4%) individuals in this cohort. Notably, 371 clinically reportable variants in PIK3CA were identified in 368 patients, constituting approximately 49.2% of all patients with reportable findings. Variants in the C2 domain of p110α are enriched in DoSM (this cohort) compared with those of cancer (Catalogue of Somatic Mutations in Cancer [COSMIC] database), highlighting the role of the C2 domain in driving uncontrolled cell proliferation in DoSM. Furthermore, we report 17 novel variants in PIK3CA that are not previously reported in DoSM and describe clinical presentation correlation for 4 novel variants. Conclusion: Our findings from the largest single-center cohort of patients with DoSM expand the spectrum of variants in PIK3CA and shed light on the less-studied role of the C2 domain in the pathogenesis of DoSM. NGS PIK3CA PIK3CA-related overgrowth spectrum PROS Somatic mosaicism Genetics Medicine R Patricia V. Hernandez verfasserin aut Michael J. Evenson verfasserin aut Meagan M. Corliss verfasserin aut Sarah L. Stein verfasserin aut Amy Theos verfasserin aut Carrie C. Coughlin verfasserin aut Bryan Sisk verfasserin aut Maithilee Menezes verfasserin aut Molly C. Schroeder verfasserin aut Jonathan W. Heusel verfasserin aut Julie A. Neidich verfasserin aut Yang Cao verfasserin aut In Genetics in Medicine Open 1(2023), 1, Seite 100815- volume:1 year:2023 number:1 pages:100815- https://doi.org/10.1016/j.gimo.2023.100815 kostenfrei https://doaj.org/article/8ea711a209f14e6298e7a8cde88994e4 kostenfrei http://www.sciencedirect.com/science/article/pii/S2949774423008245 kostenfrei https://doaj.org/toc/2949-7744 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ AR 1 2023 1 100815- |
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Bahareh A. Mojarad @@aut@@ Patricia V. Hernandez @@aut@@ Michael J. Evenson @@aut@@ Meagan M. Corliss @@aut@@ Sarah L. Stein @@aut@@ Amy Theos @@aut@@ Carrie C. Coughlin @@aut@@ Bryan Sisk @@aut@@ Maithilee Menezes @@aut@@ Molly C. Schroeder @@aut@@ Jonathan W. Heusel @@aut@@ Julie A. Neidich @@aut@@ Yang Cao @@aut@@ |
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Bahareh A. Mojarad |
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Bahareh A. Mojarad misc QH426-470 misc NGS misc PIK3CA misc PIK3CA-related overgrowth spectrum misc PROS misc Somatic mosaicism misc Genetics misc Medicine misc R Profiling PIK3CA variants in disorders of somatic mosaicism |
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Bahareh A. Mojarad Patricia V. Hernandez Michael J. Evenson Meagan M. Corliss Sarah L. Stein Amy Theos Carrie C. Coughlin Bryan Sisk Maithilee Menezes Molly C. Schroeder Jonathan W. Heusel Julie A. Neidich Yang Cao |
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profiling pik3ca variants in disorders of somatic mosaicism |
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Profiling PIK3CA variants in disorders of somatic mosaicism |
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Purpose: Variants in PIK3CA (encoding p110α; the catalytic subunit of PI3K) characterize some disorders of somatic mosaicism (DoSM) conditions with clinical features, including sporadic overgrowth and vascular malformations. Here, we profile PIK3CA variants in DoSM. Methods: We applied a next-generation, sequencing-based, laboratory-developed test, using an average coverage of approximately 2000× for up to 37 genes associated with DoSM, on a cohort of 1197 patients with DoSM referred for clinical genomics services between 2013 and 2022. Results: We identified clinically reportable variants in 747 (62.4%) individuals in this cohort. Notably, 371 clinically reportable variants in PIK3CA were identified in 368 patients, constituting approximately 49.2% of all patients with reportable findings. Variants in the C2 domain of p110α are enriched in DoSM (this cohort) compared with those of cancer (Catalogue of Somatic Mutations in Cancer [COSMIC] database), highlighting the role of the C2 domain in driving uncontrolled cell proliferation in DoSM. Furthermore, we report 17 novel variants in PIK3CA that are not previously reported in DoSM and describe clinical presentation correlation for 4 novel variants. Conclusion: Our findings from the largest single-center cohort of patients with DoSM expand the spectrum of variants in PIK3CA and shed light on the less-studied role of the C2 domain in the pathogenesis of DoSM. |
| abstractGer |
Purpose: Variants in PIK3CA (encoding p110α; the catalytic subunit of PI3K) characterize some disorders of somatic mosaicism (DoSM) conditions with clinical features, including sporadic overgrowth and vascular malformations. Here, we profile PIK3CA variants in DoSM. Methods: We applied a next-generation, sequencing-based, laboratory-developed test, using an average coverage of approximately 2000× for up to 37 genes associated with DoSM, on a cohort of 1197 patients with DoSM referred for clinical genomics services between 2013 and 2022. Results: We identified clinically reportable variants in 747 (62.4%) individuals in this cohort. Notably, 371 clinically reportable variants in PIK3CA were identified in 368 patients, constituting approximately 49.2% of all patients with reportable findings. Variants in the C2 domain of p110α are enriched in DoSM (this cohort) compared with those of cancer (Catalogue of Somatic Mutations in Cancer [COSMIC] database), highlighting the role of the C2 domain in driving uncontrolled cell proliferation in DoSM. Furthermore, we report 17 novel variants in PIK3CA that are not previously reported in DoSM and describe clinical presentation correlation for 4 novel variants. Conclusion: Our findings from the largest single-center cohort of patients with DoSM expand the spectrum of variants in PIK3CA and shed light on the less-studied role of the C2 domain in the pathogenesis of DoSM. |
| abstract_unstemmed |
Purpose: Variants in PIK3CA (encoding p110α; the catalytic subunit of PI3K) characterize some disorders of somatic mosaicism (DoSM) conditions with clinical features, including sporadic overgrowth and vascular malformations. Here, we profile PIK3CA variants in DoSM. Methods: We applied a next-generation, sequencing-based, laboratory-developed test, using an average coverage of approximately 2000× for up to 37 genes associated with DoSM, on a cohort of 1197 patients with DoSM referred for clinical genomics services between 2013 and 2022. Results: We identified clinically reportable variants in 747 (62.4%) individuals in this cohort. Notably, 371 clinically reportable variants in PIK3CA were identified in 368 patients, constituting approximately 49.2% of all patients with reportable findings. Variants in the C2 domain of p110α are enriched in DoSM (this cohort) compared with those of cancer (Catalogue of Somatic Mutations in Cancer [COSMIC] database), highlighting the role of the C2 domain in driving uncontrolled cell proliferation in DoSM. Furthermore, we report 17 novel variants in PIK3CA that are not previously reported in DoSM and describe clinical presentation correlation for 4 novel variants. Conclusion: Our findings from the largest single-center cohort of patients with DoSM expand the spectrum of variants in PIK3CA and shed light on the less-studied role of the C2 domain in the pathogenesis of DoSM. |
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Patricia V. Hernandez Michael J. Evenson Meagan M. Corliss Sarah L. Stein Amy Theos Carrie C. Coughlin Bryan Sisk Maithilee Menezes Molly C. Schroeder Jonathan W. Heusel Julie A. Neidich Yang Cao |
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