Ongoing hypermutation in the Ig V(D)J gene segments and c-myc proto-oncogene of an AIDS lymphoma segregates with neoplastic B cells at different sites: Implications for clonal evolution

Hideyuki Ikematsu, Andrea Cerutti, Hong Zan, Daniel M. Knowles, Wataru Ikematsu, Paolo Casali

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

To investigate the role of somatic Ig hypermutation in the evolution of AIDS-associated B cell lymphomas, we analyzed the Ig V(D)J and c-myc genes expressed by neoplastic B cells in two extranodal sites, testis and orbit, and clonally related cells in the bone marrow. Testis and orbit B cells expressed differentially mutated but collinear VHDJH, VκJκ and c-myc gene sequences. Shared mutations accounted for 10.2%, 8.4%, and 4.3% of the overall VHDJH, VκJκ, and c-myc gene sequences. Tumor-site specific VHDJH, VκJκ, and c-myc mutations were comparable in frequency, and a single point-mutation gave rise to an EcoRI site in the testis c-myc DNA. Both shared and tumor site-specific VHDJH, VκJκ, and c-myc mutations displayed predominance of transitions over transversions. The "neoplastic" VHDJH sequence was expressed by about 10-5 cells in the bone marrow, and contained two of the three orbital, but none of the testicular VHDJH mutations. The nature and distribution of the Ig V(D)J mutations found in the κ chain suggested a selection by antigen in testis and orbit. Our data suggest that, in AIDS-associated B cell lymphomas, the Ig hypermutation machinery targets VHDJH, VκJκ, and c-myc genes with comparable efficiency and modalities.

Original languageEnglish (US)
Pages (from-to)1242-1253
Number of pages12
JournalHuman Immunology
Volume61
Issue number12
DOIs
StatePublished - Dec 1 2000
Externally publishedYes

Fingerprint

Clonal Evolution
myc Genes
Lymphoma
Acquired Immunodeficiency Syndrome
B-Lymphocytes
Testis
Orbit
Mutation
AIDS-Related Lymphoma
Genes
B-Cell Lymphoma
Bone Marrow Cells
Immunoglobulin Somatic Hypermutation
Dilatation and Curettage
Point Mutation
Neoplasms
Antigens
DNA

Keywords

  • AIDS-associated Burkitt's lymphoma
  • B lymphocytes
  • c-myc genes
  • Somatic mutations
  • V(D)J genes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Ongoing hypermutation in the Ig V(D)J gene segments and c-myc proto-oncogene of an AIDS lymphoma segregates with neoplastic B cells at different sites : Implications for clonal evolution. / Ikematsu, Hideyuki; Cerutti, Andrea; Zan, Hong; Knowles, Daniel M.; Ikematsu, Wataru; Casali, Paolo.

In: Human Immunology, Vol. 61, No. 12, 01.12.2000, p. 1242-1253.

Research output: Contribution to journalArticle

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abstract = "To investigate the role of somatic Ig hypermutation in the evolution of AIDS-associated B cell lymphomas, we analyzed the Ig V(D)J and c-myc genes expressed by neoplastic B cells in two extranodal sites, testis and orbit, and clonally related cells in the bone marrow. Testis and orbit B cells expressed differentially mutated but collinear VHDJH, VκJκ and c-myc gene sequences. Shared mutations accounted for 10.2{\%}, 8.4{\%}, and 4.3{\%} of the overall VHDJH, VκJκ, and c-myc gene sequences. Tumor-site specific VHDJH, VκJκ, and c-myc mutations were comparable in frequency, and a single point-mutation gave rise to an EcoRI site in the testis c-myc DNA. Both shared and tumor site-specific VHDJH, VκJκ, and c-myc mutations displayed predominance of transitions over transversions. The {"}neoplastic{"} VHDJH sequence was expressed by about 10-5 cells in the bone marrow, and contained two of the three orbital, but none of the testicular VHDJH mutations. The nature and distribution of the Ig V(D)J mutations found in the κ chain suggested a selection by antigen in testis and orbit. Our data suggest that, in AIDS-associated B cell lymphomas, the Ig hypermutation machinery targets VHDJH, VκJκ, and c-myc genes with comparable efficiency and modalities.",
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