Lymphoma and plasma cell neoplasms
Molecular analysis

Topic Completed: 1 February 2011

Revised: 5 February 2019

Copyright: (c) 2001-2018,, Inc.

PubMed Search: molecular analysis lymphoma

Nikhil Sangle, M.D.
Page views in 2018: 196
Page views in 2019 to date: 167
Cite this page: Sangle N. Theory of molecular analysis. website. Accessed September 16th, 2019.
Lymphocyte Physiology
  • B cells express surface immunoglobulin (Ig), composed of 2 heavy (H) and 2 light (L) chains (either kappa or lambda)
  • T cell receptors (TCR) are either alpha / beta (95%) or gamma / delta (5%) heterodimers
  • An estimated 100 million different Ig and TCR exist, due to various physiologic mechanisms that create diversity
  • Ig and TCR germline configuration contains Variable, Diversity, Joining and Constant region segments
  • Early in normal lymphocyte differentiation within the bone marrow, the antigen receptor genes undergo recombination to create a variable region, containing an antigen combining site and a constant region
  • Diversity occurs through recombination of segments plus imprecise V-D-J joining
  • Terminal deoxytransferase (TdT) adds or removes nucleotides, causing even more diversity
  • Point mutations in V and J regions occurs commonly within Ig genes, adding to diversity
  • Reference: Arch Pathol Lab Med 1999;123:1189
Diagrams / tables

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Immunoglobulin gene rearrangement

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immunoglobulin heavy and light chain genes

Germline configuration of TCR genes

Immunoglobulin heavy chain gene rearrangement

  • Rearrangement forms a distinct band if multiple cells have the same rearrangement pattern, indicating clonality
  • 80% of B or T cell lymphomas with characteristic immunologic and clinical features have clonal IgH or TCR gamma rearrangement by PCR (Mod Pathol 2000;13:1269)
  • 10% of B cell and T cell lymphomas have both clonal IgH and TCR gamma rearrangements
  • Note: nonneoplastic tissue may be clonal, due to autoimmune diseases for B cell disorders or granulomatous diseases for T cell disorders; tissue with a small number of polyclonal B cells (skin, GI) may cause a pseudoclonal PCR profile; best to do multiple PCR and look for same rearranged band in every experiment
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