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Relative frequency and clinicopathologic characteristics of MYC-rearranged follicular lymphoma
MYC rearrangement is a relatively rare genetic abnormality in follicular lymphoma (FL). In this study, we evaluated the relative frequency of MYC rearrangement in 522 cases of FL and studied their clinicopathologic, cytogenetic, and molecular characteristics. Fluorescence in situ hybridization studi...
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| Published in: | Human pathology 2021-08, Vol.114, p.19-27 |
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| creator | Chaudhary, Shweta Brown, Noah Song, Joo Y. Yang, Lin Skrabek, Pamela Nasr, Michel R. Wong, Jerry T. Bedell, Victoria Murata-Collins, Joyce Kochan, Lindsay Li, Jie Zhang, Weiwei Chan, Wing C. Weisenburger, Dennis D. Perry, Anamarija M. |
| description | MYC rearrangement is a relatively rare genetic abnormality in follicular lymphoma (FL). In this study, we evaluated the relative frequency of MYC rearrangement in 522 cases of FL and studied their clinicopathologic, cytogenetic, and molecular characteristics. Fluorescence in situ hybridization studies for MYC (break-apart probe), MYC/IGH, IGH/BCL2, and BCL6 rearrangements were performed on tissue microarrays. Immunohistochemical stains for CD10, BCL2, BCL6, and MYC were performed and scored on MYC-rearranged cases. On 4 FL cases, a custom targeted panel of 356 genes was used for mutation analysis. Ten cases (1.9%) were positive for MYC rearrangement. Histologically, 6 of 10 cases were grade 1–2, and 4 cases were grade 3A. By immunohistochemistry, 9 of 9 tested cases were CD10+, all cases were BCL6+, and 9/10 cases were BCL2+. MYC protein staining was low in all cases tested. IGH/BCL2 rearrangement was detected in 5 of 9 cases, whereas BCL6 rearrangement was detected in 3 of 7 tested cases and 4 of 10 cases showed MYC/IGH rearrangement. The most commonly detected mutations in the MYC-positive cases included HLA-B, TNFRSF14, and KMT2D. MYC and/or B2M abnormalities were detected in 2 cases. In conclusion, MYC rearrangement is uncommon in FL and these cases do not appear to have specific histologic characteristics. Molecular analysis showed abnormalities in genes associated with transformation, namely MYC and B2M. Larger studies are needed to evaluate if MYC-rearrangement in FL has prognostic significance. |
| doi_str_mv | 10.1016/j.humpath.2021.04.014 |
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In this study, we evaluated the relative frequency of MYC rearrangement in 522 cases of FL and studied their clinicopathologic, cytogenetic, and molecular characteristics. Fluorescence in situ hybridization studies for MYC (break-apart probe), MYC/IGH, IGH/BCL2, and BCL6 rearrangements were performed on tissue microarrays. Immunohistochemical stains for CD10, BCL2, BCL6, and MYC were performed and scored on MYC-rearranged cases. On 4 FL cases, a custom targeted panel of 356 genes was used for mutation analysis. Ten cases (1.9%) were positive for MYC rearrangement. Histologically, 6 of 10 cases were grade 1–2, and 4 cases were grade 3A. By immunohistochemistry, 9 of 9 tested cases were CD10+, all cases were BCL6+, and 9/10 cases were BCL2+. MYC protein staining was low in all cases tested. IGH/BCL2 rearrangement was detected in 5 of 9 cases, whereas BCL6 rearrangement was detected in 3 of 7 tested cases and 4 of 10 cases showed MYC/IGH rearrangement. The most commonly detected mutations in the MYC-positive cases included HLA-B, TNFRSF14, and KMT2D. MYC and/or B2M abnormalities were detected in 2 cases. In conclusion, MYC rearrangement is uncommon in FL and these cases do not appear to have specific histologic characteristics. Molecular analysis showed abnormalities in genes associated with transformation, namely MYC and B2M. Larger studies are needed to evaluate if MYC-rearrangement in FL has prognostic significance.</description><identifier>ISSN: 0046-8177</identifier><identifier>EISSN: 1532-8392</identifier><identifier>DOI: 10.1016/j.humpath.2021.04.014</identifier><identifier>PMID: 33964277</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Adult ; Aged ; Aged, 80 and over ; BCL2 rearrangement ; Biomarkers, Tumor - analysis ; Biomarkers, Tumor - genetics ; Cancer ; DNA Mutational Analysis ; Double-hit lymphoma ; Female ; Follicular lymphoma ; Gene Rearrangement ; Genes ; Genomes ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Lymphoma ; Lymphoma, Follicular - chemistry ; Lymphoma, Follicular - drug therapy ; Lymphoma, Follicular - genetics ; Lymphoma, Follicular - pathology ; Male ; Manitoba ; Medical prognosis ; Middle Aged ; Mutation ; MYC rearrangement ; Prognosis ; Proto-Oncogene Proteins c-myc - analysis ; Proto-Oncogene Proteins c-myc - genetics ; Software ; Tissue Array Analysis ; United States</subject><ispartof>Human pathology, 2021-08, Vol.114, p.19-27</ispartof><rights>2021 Elsevier Inc.</rights><rights>Copyright © 2021 Elsevier Inc. All rights reserved.</rights><rights>2021. Elsevier Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c459t-bf8c451ae16ac01aad0584eaf6edac5498a79b68e278342fbbdb8ef45b5ca0813</citedby><cites>FETCH-LOGICAL-c459t-bf8c451ae16ac01aad0584eaf6edac5498a79b68e278342fbbdb8ef45b5ca0813</cites><orcidid>0000-0002-3343-5698 ; 0000-0002-0727-2784 ; 0000-0003-2480-0443 ; 0000-0002-5700-2141</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27922,27923</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33964277$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chaudhary, Shweta</creatorcontrib><creatorcontrib>Brown, Noah</creatorcontrib><creatorcontrib>Song, Joo Y.</creatorcontrib><creatorcontrib>Yang, Lin</creatorcontrib><creatorcontrib>Skrabek, Pamela</creatorcontrib><creatorcontrib>Nasr, Michel R.</creatorcontrib><creatorcontrib>Wong, Jerry T.</creatorcontrib><creatorcontrib>Bedell, Victoria</creatorcontrib><creatorcontrib>Murata-Collins, Joyce</creatorcontrib><creatorcontrib>Kochan, Lindsay</creatorcontrib><creatorcontrib>Li, Jie</creatorcontrib><creatorcontrib>Zhang, Weiwei</creatorcontrib><creatorcontrib>Chan, Wing C.</creatorcontrib><creatorcontrib>Weisenburger, Dennis D.</creatorcontrib><creatorcontrib>Perry, Anamarija M.</creatorcontrib><title>Relative frequency and clinicopathologic characteristics of MYC-rearranged follicular lymphoma</title><title>Human pathology</title><addtitle>Hum Pathol</addtitle><description>MYC rearrangement is a relatively rare genetic abnormality in follicular lymphoma (FL). In this study, we evaluated the relative frequency of MYC rearrangement in 522 cases of FL and studied their clinicopathologic, cytogenetic, and molecular characteristics. Fluorescence in situ hybridization studies for MYC (break-apart probe), MYC/IGH, IGH/BCL2, and BCL6 rearrangements were performed on tissue microarrays. Immunohistochemical stains for CD10, BCL2, BCL6, and MYC were performed and scored on MYC-rearranged cases. On 4 FL cases, a custom targeted panel of 356 genes was used for mutation analysis. Ten cases (1.9%) were positive for MYC rearrangement. Histologically, 6 of 10 cases were grade 1–2, and 4 cases were grade 3A. By immunohistochemistry, 9 of 9 tested cases were CD10+, all cases were BCL6+, and 9/10 cases were BCL2+. MYC protein staining was low in all cases tested. IGH/BCL2 rearrangement was detected in 5 of 9 cases, whereas BCL6 rearrangement was detected in 3 of 7 tested cases and 4 of 10 cases showed MYC/IGH rearrangement. The most commonly detected mutations in the MYC-positive cases included HLA-B, TNFRSF14, and KMT2D. MYC and/or B2M abnormalities were detected in 2 cases. In conclusion, MYC rearrangement is uncommon in FL and these cases do not appear to have specific histologic characteristics. Molecular analysis showed abnormalities in genes associated with transformation, namely MYC and B2M. Larger studies are needed to evaluate if MYC-rearrangement in FL has prognostic significance.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>BCL2 rearrangement</subject><subject>Biomarkers, Tumor - analysis</subject><subject>Biomarkers, Tumor - genetics</subject><subject>Cancer</subject><subject>DNA Mutational Analysis</subject><subject>Double-hit lymphoma</subject><subject>Female</subject><subject>Follicular lymphoma</subject><subject>Gene Rearrangement</subject><subject>Genes</subject><subject>Genomes</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>In Situ Hybridization, Fluorescence</subject><subject>Lymphoma</subject><subject>Lymphoma, Follicular - chemistry</subject><subject>Lymphoma, Follicular - drug therapy</subject><subject>Lymphoma, Follicular - genetics</subject><subject>Lymphoma, Follicular - pathology</subject><subject>Male</subject><subject>Manitoba</subject><subject>Medical prognosis</subject><subject>Middle Aged</subject><subject>Mutation</subject><subject>MYC rearrangement</subject><subject>Prognosis</subject><subject>Proto-Oncogene Proteins c-myc - analysis</subject><subject>Proto-Oncogene Proteins c-myc - genetics</subject><subject>Software</subject><subject>Tissue Array Analysis</subject><subject>United States</subject><issn>0046-8177</issn><issn>1532-8392</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><recordid>eNqFkUFv1DAQha2Kim4LP6EoEhcuSW3HTpwTQiuglYqQUDlwwZo4465XTrzYSaX99_Vqlx64cJo5fDNv5j1CrhmtGGXNzbbaLOMO5k3FKWcVFRVl4oysmKx5qeqOvyIrSkVTKta2F-QypS2ljEkhX5OLuu4awdt2RX7_QA-ze8LCRvyz4GT2BUxDYbybnAkHgeDDozOF2UAEM2N0aXYmFcEW336ty4gQI0yPOBQ2eO_M4iEWfj_uNmGEN-Tcgk_49lSvyM8vnx_Wt-X9969360_3pRGym8veqtwwQNaAoQxgoFIJBNvgAEaKTkHb9Y1C3qpacNv3Q6_QCtlLA1Sx-op8OO7dxZC_SLMeXTLoPUwYlqS55EIpqhqa0ff_oNuwxClfl6msKljXNpmSR8rEkFJEq3fRjRD3mlF9CEBv9SkAfQhAU6FzAHnu3Wn70o84vEz9dTwDH48AZjueHEadjMu24-AimlkPwf1H4hmGlJus</recordid><startdate>202108</startdate><enddate>202108</enddate><creator>Chaudhary, Shweta</creator><creator>Brown, Noah</creator><creator>Song, Joo Y.</creator><creator>Yang, Lin</creator><creator>Skrabek, Pamela</creator><creator>Nasr, Michel R.</creator><creator>Wong, Jerry T.</creator><creator>Bedell, Victoria</creator><creator>Murata-Collins, Joyce</creator><creator>Kochan, Lindsay</creator><creator>Li, Jie</creator><creator>Zhang, Weiwei</creator><creator>Chan, Wing C.</creator><creator>Weisenburger, Dennis D.</creator><creator>Perry, Anamarija M.</creator><general>Elsevier Inc</general><general>Elsevier Limited</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>K9.</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-3343-5698</orcidid><orcidid>https://orcid.org/0000-0002-0727-2784</orcidid><orcidid>https://orcid.org/0000-0003-2480-0443</orcidid><orcidid>https://orcid.org/0000-0002-5700-2141</orcidid></search><sort><creationdate>202108</creationdate><title>Relative frequency and clinicopathologic characteristics of MYC-rearranged follicular lymphoma</title><author>Chaudhary, Shweta ; Brown, Noah ; Song, Joo Y. ; Yang, Lin ; Skrabek, Pamela ; Nasr, Michel R. ; Wong, Jerry T. ; Bedell, Victoria ; Murata-Collins, Joyce ; Kochan, Lindsay ; Li, Jie ; Zhang, Weiwei ; Chan, Wing C. ; Weisenburger, Dennis D. ; Perry, Anamarija M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c459t-bf8c451ae16ac01aad0584eaf6edac5498a79b68e278342fbbdb8ef45b5ca0813</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>BCL2 rearrangement</topic><topic>Biomarkers, Tumor - analysis</topic><topic>Biomarkers, Tumor - genetics</topic><topic>Cancer</topic><topic>DNA Mutational Analysis</topic><topic>Double-hit lymphoma</topic><topic>Female</topic><topic>Follicular lymphoma</topic><topic>Gene Rearrangement</topic><topic>Genes</topic><topic>Genomes</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>In Situ Hybridization, Fluorescence</topic><topic>Lymphoma</topic><topic>Lymphoma, Follicular - chemistry</topic><topic>Lymphoma, Follicular - drug therapy</topic><topic>Lymphoma, Follicular - genetics</topic><topic>Lymphoma, Follicular - pathology</topic><topic>Male</topic><topic>Manitoba</topic><topic>Medical prognosis</topic><topic>Middle Aged</topic><topic>Mutation</topic><topic>MYC rearrangement</topic><topic>Prognosis</topic><topic>Proto-Oncogene Proteins c-myc - analysis</topic><topic>Proto-Oncogene Proteins c-myc - genetics</topic><topic>Software</topic><topic>Tissue Array Analysis</topic><topic>United States</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chaudhary, Shweta</creatorcontrib><creatorcontrib>Brown, Noah</creatorcontrib><creatorcontrib>Song, Joo Y.</creatorcontrib><creatorcontrib>Yang, Lin</creatorcontrib><creatorcontrib>Skrabek, Pamela</creatorcontrib><creatorcontrib>Nasr, Michel R.</creatorcontrib><creatorcontrib>Wong, Jerry T.</creatorcontrib><creatorcontrib>Bedell, Victoria</creatorcontrib><creatorcontrib>Murata-Collins, Joyce</creatorcontrib><creatorcontrib>Kochan, Lindsay</creatorcontrib><creatorcontrib>Li, Jie</creatorcontrib><creatorcontrib>Zhang, Weiwei</creatorcontrib><creatorcontrib>Chan, Wing C.</creatorcontrib><creatorcontrib>Weisenburger, Dennis D.</creatorcontrib><creatorcontrib>Perry, Anamarija M.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Human pathology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chaudhary, Shweta</au><au>Brown, Noah</au><au>Song, Joo Y.</au><au>Yang, Lin</au><au>Skrabek, Pamela</au><au>Nasr, Michel R.</au><au>Wong, Jerry T.</au><au>Bedell, Victoria</au><au>Murata-Collins, Joyce</au><au>Kochan, Lindsay</au><au>Li, Jie</au><au>Zhang, Weiwei</au><au>Chan, Wing C.</au><au>Weisenburger, Dennis D.</au><au>Perry, Anamarija M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Relative frequency and clinicopathologic characteristics of MYC-rearranged follicular lymphoma</atitle><jtitle>Human pathology</jtitle><addtitle>Hum Pathol</addtitle><date>2021-08</date><risdate>2021</risdate><volume>114</volume><spage>19</spage><epage>27</epage><pages>19-27</pages><issn>0046-8177</issn><eissn>1532-8392</eissn><abstract>MYC rearrangement is a relatively rare genetic abnormality in follicular lymphoma (FL). In this study, we evaluated the relative frequency of MYC rearrangement in 522 cases of FL and studied their clinicopathologic, cytogenetic, and molecular characteristics. Fluorescence in situ hybridization studies for MYC (break-apart probe), MYC/IGH, IGH/BCL2, and BCL6 rearrangements were performed on tissue microarrays. Immunohistochemical stains for CD10, BCL2, BCL6, and MYC were performed and scored on MYC-rearranged cases. On 4 FL cases, a custom targeted panel of 356 genes was used for mutation analysis. Ten cases (1.9%) were positive for MYC rearrangement. Histologically, 6 of 10 cases were grade 1–2, and 4 cases were grade 3A. By immunohistochemistry, 9 of 9 tested cases were CD10+, all cases were BCL6+, and 9/10 cases were BCL2+. MYC protein staining was low in all cases tested. IGH/BCL2 rearrangement was detected in 5 of 9 cases, whereas BCL6 rearrangement was detected in 3 of 7 tested cases and 4 of 10 cases showed MYC/IGH rearrangement. The most commonly detected mutations in the MYC-positive cases included HLA-B, TNFRSF14, and KMT2D. MYC and/or B2M abnormalities were detected in 2 cases. In conclusion, MYC rearrangement is uncommon in FL and these cases do not appear to have specific histologic characteristics. Molecular analysis showed abnormalities in genes associated with transformation, namely MYC and B2M. Larger studies are needed to evaluate if MYC-rearrangement in FL has prognostic significance.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>33964277</pmid><doi>10.1016/j.humpath.2021.04.014</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0002-3343-5698</orcidid><orcidid>https://orcid.org/0000-0002-0727-2784</orcidid><orcidid>https://orcid.org/0000-0003-2480-0443</orcidid><orcidid>https://orcid.org/0000-0002-5700-2141</orcidid></addata></record> |
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| subjects | Adult Aged Aged, 80 and over BCL2 rearrangement Biomarkers, Tumor - analysis Biomarkers, Tumor - genetics Cancer DNA Mutational Analysis Double-hit lymphoma Female Follicular lymphoma Gene Rearrangement Genes Genomes Humans Immunohistochemistry In Situ Hybridization, Fluorescence Lymphoma Lymphoma, Follicular - chemistry Lymphoma, Follicular - drug therapy Lymphoma, Follicular - genetics Lymphoma, Follicular - pathology Male Manitoba Medical prognosis Middle Aged Mutation MYC rearrangement Prognosis Proto-Oncogene Proteins c-myc - analysis Proto-Oncogene Proteins c-myc - genetics Software Tissue Array Analysis United States |
| title | Relative frequency and clinicopathologic characteristics of MYC-rearranged follicular lymphoma |
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