Lymphoma and plasma cell neoplasms
Molecular analysis
Theory

Author: Nikhil Sangle, M.D. (see Authors page)

Revised: 3 April 2017, last major update February 2011

Copyright: (c) 2001-2017, PathologyOutlines.com, Inc.

PubMed Search: molecular analysis lymphoma

Cite this page: Theory of molecular analysis. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/lymphomamoleculartheory.html. Accessed December 17th, 2017.
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

Clonality
  • 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
Gel Images

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Clonally arranged B cell populations

Clonal T cell population

Reactive (not clonal) cell population