Mutations in JAK/STAT and NOTCH1 Genes Are Enriched in Post-Transplant Lymphoproliferative Disorders
Post-transplant lymphoproliferative disorders (PTLD) are diseases occurring in immunocompromised patients after hematopoietic stem cell transplantation (HCT) or solid organ transplantation (SOT). Although PTLD occurs rarely, it may be associated with poor outcomes. In most cases, PTLD is driven by E...
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| Format: | Article |
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Frontiers Media S.A.
2022-01-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2021.790481/full |
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| author | Alexandra Butzmann Alexandra Butzmann Kaushik Sridhar Diwash Jangam Hanbing Song Amol Singh Jyoti Kumar Karen M. Chisholm Benjamin Pinsky Franklin Huang Robert S. Ohgami |
| author_facet | Alexandra Butzmann Alexandra Butzmann Kaushik Sridhar Diwash Jangam Hanbing Song Amol Singh Jyoti Kumar Karen M. Chisholm Benjamin Pinsky Franklin Huang Robert S. Ohgami |
| author_sort | Alexandra Butzmann |
| collection | DOAJ |
| description | Post-transplant lymphoproliferative disorders (PTLD) are diseases occurring in immunocompromised patients after hematopoietic stem cell transplantation (HCT) or solid organ transplantation (SOT). Although PTLD occurs rarely, it may be associated with poor outcomes. In most cases, PTLD is driven by Epstein-Barr virus (EBV) infection. Few studies have investigated the mutational landscape and gene expression profile of PTLD. In our study, we performed targeted deep sequencing and RNA-sequencing (RNA-Seq) on 16 cases of florid follicular hyperplasia (FFH) type PTLD and 15 cases of other PTLD types that include: ten monomorphic (M-PTLD), three polymorphic (P-PTLD), and two classic Hodgkin lymphoma type PTLDs (CHL-PTLD). Our study identified recurrent mutations in JAK3 in five of 15 PTLD cases and one of 16 FFH-PTLD cases, as well as 16 other genes that were mutated in M-PTLD, P-PTLD, CHL-PTLD and FFH-PTLD. Digital image analysis demonstrated significant differences in single cell area, major axis, and diameter when comparing cases of M-PTLD and P-PTLD to FFH-PTLD. No morphometric relationship was identified with regards to a specific genetic mutation. Our findings suggest that immune regulatory pathways play an essential role in PTLD, with the JAK/STAT pathway affected in many PTLDs. |
| first_indexed | 2024-04-11T18:22:48Z |
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| id | doaj.art-16330ea7f6f941179cf86195dd2203b7 |
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| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-11T18:22:48Z |
| publishDate | 2022-01-01 |
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| series | Frontiers in Oncology |
| spelling | doaj.art-16330ea7f6f941179cf86195dd2203b72022-12-22T04:09:43ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-01-011110.3389/fonc.2021.790481790481Mutations in JAK/STAT and NOTCH1 Genes Are Enriched in Post-Transplant Lymphoproliferative DisordersAlexandra Butzmann0Alexandra Butzmann1Kaushik Sridhar2Diwash Jangam3Hanbing Song4Amol Singh5Jyoti Kumar6Karen M. Chisholm7Benjamin Pinsky8Franklin Huang9Robert S. Ohgami10Agilent Technologies, Santa Clara, CA, United StatesDepartment of Pathology, University of California, San Francisco, San Francisco, CA, United StatesDepartment of Pathology, University of California, San Francisco, San Francisco, CA, United StatesDepartment of Pathology, Stanford University, Stanford, CA, United StatesDepartment of Pathology, University of California, San Francisco, San Francisco, CA, United StatesDepartment of Pathology, Stanford University, Stanford, CA, United StatesDepartment of Pathology, Stanford University, Stanford, CA, United StatesDepartment of Laboratories, Seattle Children’s Hospital, Seattle, WA, United StatesDepartment of Pathology, Stanford University, Stanford, CA, United StatesDepartment of Pathology, University of California, San Francisco, San Francisco, CA, United StatesDepartment of Pathology, University of California, San Francisco, San Francisco, CA, United StatesPost-transplant lymphoproliferative disorders (PTLD) are diseases occurring in immunocompromised patients after hematopoietic stem cell transplantation (HCT) or solid organ transplantation (SOT). Although PTLD occurs rarely, it may be associated with poor outcomes. In most cases, PTLD is driven by Epstein-Barr virus (EBV) infection. Few studies have investigated the mutational landscape and gene expression profile of PTLD. In our study, we performed targeted deep sequencing and RNA-sequencing (RNA-Seq) on 16 cases of florid follicular hyperplasia (FFH) type PTLD and 15 cases of other PTLD types that include: ten monomorphic (M-PTLD), three polymorphic (P-PTLD), and two classic Hodgkin lymphoma type PTLDs (CHL-PTLD). Our study identified recurrent mutations in JAK3 in five of 15 PTLD cases and one of 16 FFH-PTLD cases, as well as 16 other genes that were mutated in M-PTLD, P-PTLD, CHL-PTLD and FFH-PTLD. Digital image analysis demonstrated significant differences in single cell area, major axis, and diameter when comparing cases of M-PTLD and P-PTLD to FFH-PTLD. No morphometric relationship was identified with regards to a specific genetic mutation. Our findings suggest that immune regulatory pathways play an essential role in PTLD, with the JAK/STAT pathway affected in many PTLDs.https://www.frontiersin.org/articles/10.3389/fonc.2021.790481/fullPTLDEpstein-Barr Virus (EBV)florid follicular hyperplasiatargeted sequencingnext generation (deep) sequencing (NGS)whole transcriptome sequencing |
| spellingShingle | Alexandra Butzmann Alexandra Butzmann Kaushik Sridhar Diwash Jangam Hanbing Song Amol Singh Jyoti Kumar Karen M. Chisholm Benjamin Pinsky Franklin Huang Robert S. Ohgami Mutations in JAK/STAT and NOTCH1 Genes Are Enriched in Post-Transplant Lymphoproliferative Disorders Frontiers in Oncology PTLD Epstein-Barr Virus (EBV) florid follicular hyperplasia targeted sequencing next generation (deep) sequencing (NGS) whole transcriptome sequencing |
| title | Mutations in JAK/STAT and NOTCH1 Genes Are Enriched in Post-Transplant Lymphoproliferative Disorders |
| title_full | Mutations in JAK/STAT and NOTCH1 Genes Are Enriched in Post-Transplant Lymphoproliferative Disorders |
| title_fullStr | Mutations in JAK/STAT and NOTCH1 Genes Are Enriched in Post-Transplant Lymphoproliferative Disorders |
| title_full_unstemmed | Mutations in JAK/STAT and NOTCH1 Genes Are Enriched in Post-Transplant Lymphoproliferative Disorders |
| title_short | Mutations in JAK/STAT and NOTCH1 Genes Are Enriched in Post-Transplant Lymphoproliferative Disorders |
| title_sort | mutations in jak stat and notch1 genes are enriched in post transplant lymphoproliferative disorders |
| topic | PTLD Epstein-Barr Virus (EBV) florid follicular hyperplasia targeted sequencing next generation (deep) sequencing (NGS) whole transcriptome sequencing |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2021.790481/full |
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