Molecular genetic analysis demonstrates that multiple posttransplantation lymphoproliferative disorders occurring in one anatomic site in a single patient represent distinct primary lymphoid neoplasms

A. Chadburn, E. Cesarman, Fang Liu Yi Fang Liu, L. Addonizio, Daphne T. Hsu, Robert E. Michler, D. M. Knowles

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Background. Posttransplantation lymphoproliferative disorders (PT-LPDs) are a clinicopathologically heterogeneous group of lymphoid proliferations of varied clonal composition, the majority of which are associated with Epstein- Barr virus (EBV) infection. The clonal content and clonal relatedness of 24 separate PT-LPD lesions occurring synchronously in one organ in a single patient were investigated. Methods. Twenty-four separate PT-LPD lesions from the colon and mesentery of a 15-year-old male, developing 4 months after cardiac transplantation, were studied for clonality based on immunoglobulin heavy chain (IgH) gene rearrangements for the presence, clonality, and type of EBV infection and for the presence of c-myc, ras, and p53 gene alterations. Southern blot hybridization, polymerase chain reaction, and single strand conformation polymorphism assays were employed. Results. All 24 lesions were histologically similar (polymorphic B-cell lymphomas) but exhibited varied clonality and were clonally distinct with respect to both IgH gene rearrangements and EBV infection. All lesions were infected with EBV type A. Structural alterations of oncogenes or tumor suppressor genes were not identified. Conclusions. Separate PT-LPD lesions occurring synchronously in a single organ or patient may be clonally distinct, suggesting that they represent multiple distinct primary lymphoid proliferations rather than metastatic disease as in conventional malignant lymphomas. This may explain partially the rapid development in some patients of a large PT-LPD tumor burden that may regress rapidly after reduction of immunosuppression.

Original languageEnglish (US)
Pages (from-to)2747-2756
Number of pages10
JournalCancer
Volume75
Issue number11
DOIs
StatePublished - 1995
Externally publishedYes

Fingerprint

Lymphoproliferative Disorders
Molecular Biology
Epstein-Barr Virus Infections
Immunoglobulin Heavy Chain Genes
Gene Rearrangement
Neoplasms
myc Genes
Mesentery
ras Genes
p53 Genes
B-Cell Lymphoma
Heart Transplantation
Southern Blotting
Tumor Burden
Tumor Suppressor Genes
Human Herpesvirus 4
Oncogenes
Immunosuppression
Lymphoma
Colon

Keywords

  • B cells
  • Epstein-Barr virus
  • malignant lymphoma
  • posttransplantation lymphoproliferative disorder
  • transplantation

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Molecular genetic analysis demonstrates that multiple posttransplantation lymphoproliferative disorders occurring in one anatomic site in a single patient represent distinct primary lymphoid neoplasms. / Chadburn, A.; Cesarman, E.; Yi Fang Liu, Fang Liu; Addonizio, L.; Hsu, Daphne T.; Michler, Robert E.; Knowles, D. M.

In: Cancer, Vol. 75, No. 11, 1995, p. 2747-2756.

Research output: Contribution to journalArticle

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abstract = "Background. Posttransplantation lymphoproliferative disorders (PT-LPDs) are a clinicopathologically heterogeneous group of lymphoid proliferations of varied clonal composition, the majority of which are associated with Epstein- Barr virus (EBV) infection. The clonal content and clonal relatedness of 24 separate PT-LPD lesions occurring synchronously in one organ in a single patient were investigated. Methods. Twenty-four separate PT-LPD lesions from the colon and mesentery of a 15-year-old male, developing 4 months after cardiac transplantation, were studied for clonality based on immunoglobulin heavy chain (IgH) gene rearrangements for the presence, clonality, and type of EBV infection and for the presence of c-myc, ras, and p53 gene alterations. Southern blot hybridization, polymerase chain reaction, and single strand conformation polymorphism assays were employed. Results. All 24 lesions were histologically similar (polymorphic B-cell lymphomas) but exhibited varied clonality and were clonally distinct with respect to both IgH gene rearrangements and EBV infection. All lesions were infected with EBV type A. Structural alterations of oncogenes or tumor suppressor genes were not identified. Conclusions. Separate PT-LPD lesions occurring synchronously in a single organ or patient may be clonally distinct, suggesting that they represent multiple distinct primary lymphoid proliferations rather than metastatic disease as in conventional malignant lymphomas. This may explain partially the rapid development in some patients of a large PT-LPD tumor burden that may regress rapidly after reduction of immunosuppression.",
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T1 - Molecular genetic analysis demonstrates that multiple posttransplantation lymphoproliferative disorders occurring in one anatomic site in a single patient represent distinct primary lymphoid neoplasms

AU - Chadburn, A.

AU - Cesarman, E.

AU - Yi Fang Liu, Fang Liu

AU - Addonizio, L.

AU - Hsu, Daphne T.

AU - Michler, Robert E.

AU - Knowles, D. M.

PY - 1995

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N2 - Background. Posttransplantation lymphoproliferative disorders (PT-LPDs) are a clinicopathologically heterogeneous group of lymphoid proliferations of varied clonal composition, the majority of which are associated with Epstein- Barr virus (EBV) infection. The clonal content and clonal relatedness of 24 separate PT-LPD lesions occurring synchronously in one organ in a single patient were investigated. Methods. Twenty-four separate PT-LPD lesions from the colon and mesentery of a 15-year-old male, developing 4 months after cardiac transplantation, were studied for clonality based on immunoglobulin heavy chain (IgH) gene rearrangements for the presence, clonality, and type of EBV infection and for the presence of c-myc, ras, and p53 gene alterations. Southern blot hybridization, polymerase chain reaction, and single strand conformation polymorphism assays were employed. Results. All 24 lesions were histologically similar (polymorphic B-cell lymphomas) but exhibited varied clonality and were clonally distinct with respect to both IgH gene rearrangements and EBV infection. All lesions were infected with EBV type A. Structural alterations of oncogenes or tumor suppressor genes were not identified. Conclusions. Separate PT-LPD lesions occurring synchronously in a single organ or patient may be clonally distinct, suggesting that they represent multiple distinct primary lymphoid proliferations rather than metastatic disease as in conventional malignant lymphomas. This may explain partially the rapid development in some patients of a large PT-LPD tumor burden that may regress rapidly after reduction of immunosuppression.

AB - Background. Posttransplantation lymphoproliferative disorders (PT-LPDs) are a clinicopathologically heterogeneous group of lymphoid proliferations of varied clonal composition, the majority of which are associated with Epstein- Barr virus (EBV) infection. The clonal content and clonal relatedness of 24 separate PT-LPD lesions occurring synchronously in one organ in a single patient were investigated. Methods. Twenty-four separate PT-LPD lesions from the colon and mesentery of a 15-year-old male, developing 4 months after cardiac transplantation, were studied for clonality based on immunoglobulin heavy chain (IgH) gene rearrangements for the presence, clonality, and type of EBV infection and for the presence of c-myc, ras, and p53 gene alterations. Southern blot hybridization, polymerase chain reaction, and single strand conformation polymorphism assays were employed. Results. All 24 lesions were histologically similar (polymorphic B-cell lymphomas) but exhibited varied clonality and were clonally distinct with respect to both IgH gene rearrangements and EBV infection. All lesions were infected with EBV type A. Structural alterations of oncogenes or tumor suppressor genes were not identified. Conclusions. Separate PT-LPD lesions occurring synchronously in a single organ or patient may be clonally distinct, suggesting that they represent multiple distinct primary lymphoid proliferations rather than metastatic disease as in conventional malignant lymphomas. This may explain partially the rapid development in some patients of a large PT-LPD tumor burden that may regress rapidly after reduction of immunosuppression.

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