Next generation sequencing of the clonal IGH rearrangement detects ongoing mutations and interfollicular trafficking in in situ follicular neoplasia
Follicular lymphoma (FL) is characterized genetically by a significant intraclonal diversity of rearranged immunoglobulin heavy chain (IGH) genes and a substantial cell migration activity (follicular trafficking). Recently, in situ follicular neoplasia (ISFN), characterized by accumulations of immun...
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| Veröffentlicht in: | PloS one 2017-06, Vol.12 (6), p.e0178503-e0178503 |
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| creator | Kosmidis, Perikles Bonzheim, Irina Dufke, Claudia Colak, Sema Hentrich, Thomas Schroeder, Christopher Bauer, Peter Adam, Patrick Fend, Falko |
| description | Follicular lymphoma (FL) is characterized genetically by a significant intraclonal diversity of rearranged immunoglobulin heavy chain (IGH) genes and a substantial cell migration activity (follicular trafficking). Recently, in situ follicular neoplasia (ISFN), characterized by accumulations of immunohistochemically strongly BCL2-positive, t(14;18)+ clonal B cells confined to germinal centers in reactive lymph nodes, has been identified as a precursor lesion of FL with low risk of progression to manifest FL. The extent of ongoing somatic hypermutation of rearranged IGH genes and interfollicular trafficking in ISFN is not known. In this study we performed an in depth analysis of clonal evolution and cell migration patterns in a case of pure ISFN involving multiple lymph nodes. Using laser microdissection and next generation sequencing (NGS) we documented significant intraclonal diversity of the rearranged IGH gene and extensive interfollicular migration between germinal centers of the same lymph node as well as between different lymph nodes. Furthermore, we identified N-glycosylation motifs characteristic for FL in the CDR3 region. |
| doi_str_mv | 10.1371/journal.pone.0178503 |
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Recently, in situ follicular neoplasia (ISFN), characterized by accumulations of immunohistochemically strongly BCL2-positive, t(14;18)+ clonal B cells confined to germinal centers in reactive lymph nodes, has been identified as a precursor lesion of FL with low risk of progression to manifest FL. The extent of ongoing somatic hypermutation of rearranged IGH genes and interfollicular trafficking in ISFN is not known. In this study we performed an in depth analysis of clonal evolution and cell migration patterns in a case of pure ISFN involving multiple lymph nodes. Using laser microdissection and next generation sequencing (NGS) we documented significant intraclonal diversity of the rearranged IGH gene and extensive interfollicular migration between germinal centers of the same lymph node as well as between different lymph nodes. 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This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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Recently, in situ follicular neoplasia (ISFN), characterized by accumulations of immunohistochemically strongly BCL2-positive, t(14;18)+ clonal B cells confined to germinal centers in reactive lymph nodes, has been identified as a precursor lesion of FL with low risk of progression to manifest FL. The extent of ongoing somatic hypermutation of rearranged IGH genes and interfollicular trafficking in ISFN is not known. In this study we performed an in depth analysis of clonal evolution and cell migration patterns in a case of pure ISFN involving multiple lymph nodes. Using laser microdissection and next generation sequencing (NGS) we documented significant intraclonal diversity of the rearranged IGH gene and extensive interfollicular migration between germinal centers of the same lymph node as well as between different lymph nodes. Furthermore, we identified N-glycosylation motifs characteristic for FL in the CDR3 region.</description><subject>Aged</subject><subject>Analysis</subject><subject>B cells</subject><subject>Biology and Life Sciences</subject><subject>Bone marrow</subject><subject>Cancer</subject><subject>Case depth</subject><subject>Cell adhesion & migration</subject><subject>Cell migration</subject><subject>Cell Movement - genetics</subject><subject>Complementarity-determining region 3</subject><subject>Computer and Information Sciences</subject><subject>DNA Mutational Analysis</subject><subject>Female</subject><subject>Gene Rearrangement</subject><subject>Gene sequencing</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>Genetics</subject><subject>Genomics</subject><subject>Germinal centers</subject><subject>Glycosylation</subject><subject>Heavy chains</subject><subject>High-Throughput Nucleotide Sequencing</subject><subject>Hospitals</subject><subject>Humans</subject><subject>Immunoglobulin Heavy Chains - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kosmidis, Perikles</au><au>Bonzheim, Irina</au><au>Dufke, Claudia</au><au>Colak, Sema</au><au>Hentrich, Thomas</au><au>Schroeder, Christopher</au><au>Bauer, Peter</au><au>Adam, Patrick</au><au>Fend, Falko</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Next generation sequencing of the clonal IGH rearrangement detects ongoing mutations and interfollicular trafficking in in situ follicular neoplasia</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2017-06-22</date><risdate>2017</risdate><volume>12</volume><issue>6</issue><spage>e0178503</spage><epage>e0178503</epage><pages>e0178503-e0178503</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Follicular lymphoma (FL) is characterized genetically by a significant intraclonal diversity of rearranged immunoglobulin heavy chain (IGH) genes and a substantial cell migration activity (follicular trafficking). Recently, in situ follicular neoplasia (ISFN), characterized by accumulations of immunohistochemically strongly BCL2-positive, t(14;18)+ clonal B cells confined to germinal centers in reactive lymph nodes, has been identified as a precursor lesion of FL with low risk of progression to manifest FL. The extent of ongoing somatic hypermutation of rearranged IGH genes and interfollicular trafficking in ISFN is not known. In this study we performed an in depth analysis of clonal evolution and cell migration patterns in a case of pure ISFN involving multiple lymph nodes. Using laser microdissection and next generation sequencing (NGS) we documented significant intraclonal diversity of the rearranged IGH gene and extensive interfollicular migration between germinal centers of the same lymph node as well as between different lymph nodes. Furthermore, we identified N-glycosylation motifs characteristic for FL in the CDR3 region.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>28640838</pmid><doi>10.1371/journal.pone.0178503</doi><tpages>e0178503</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Aged Analysis B cells Biology and Life Sciences Bone marrow Cancer Case depth Cell adhesion & migration Cell migration Cell Movement - genetics Complementarity-determining region 3 Computer and Information Sciences DNA Mutational Analysis Female Gene Rearrangement Gene sequencing Genes Genetic aspects Genetics Genomics Germinal centers Glycosylation Heavy chains High-Throughput Nucleotide Sequencing Hospitals Humans Immunoglobulin Heavy Chains - genetics Immunoglobulins Lasers Lymph nodes Lymphatic system Lymphocytes B Lymphoma Lymphoma, Follicular - genetics Lymphoma, Follicular - pathology Lymphomas Male Medicine and Health Sciences Mutation Neuropathology Pathogenesis Pathology Research and Analysis Methods Somatic hypermutation Transcription |
| title | Next generation sequencing of the clonal IGH rearrangement detects ongoing mutations and interfollicular trafficking in in situ follicular neoplasia |
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