Genomic analysis of follicular dendritic cell sarcoma by molecular inversion probe array reveals tumor suppressor-driven biology
Follicular dendritic cell sarcoma is a rare malignant neoplasm of dendritic cell origin that is currently poorly characterized by genetic studies. To investigate whether recurrent genomic alterations may underlie the biology of follicular dendritic cell sarcoma and to identify potential contributory...
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| Veröffentlicht in: | Modern pathology 2017-09, Vol.30 (9), p.1321-1334 |
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| creator | Andersen, Erica F Paxton, Christian N O'Malley, Dennis P Louissaint Jr, Abner Hornick, Jason L Griffin, Gabriel K Fedoriw, Yuri Kim, Young S Weiss, Lawrence M Perkins, Sherrie L South, Sarah T |
| description | Follicular dendritic cell sarcoma is a rare malignant neoplasm of dendritic cell origin that is currently poorly characterized by genetic studies. To investigate whether recurrent genomic alterations may underlie the biology of follicular dendritic cell sarcoma and to identify potential contributory regions and genes, molecular inversion probe array analysis was performed on 14 independent formalin-fixed, paraffin-embedded samples. Abnormal genomic profiles were observed in 11 out of 14 (79%) cases. The majority showed extensive genomic complexity that was predominantly represented by hemizygous losses affecting multiple chromosomes. Alterations of chromosomal regions 1p (55%), 2p (55%), 3p (82%), 3q (45%), 6q (55%), 7q (73%), 8p (45%), 9p (64%), 11q (64%), 13q (91%), 14q (82%), 15q (64%), 17p (55%), 18q (64%), and 22q (55%) were recurrent across the 11 samples showing abnormal genomic profiles. Many recurrent genomic alterations in follicular dendritic cell sarcoma overlap deletions that are frequently observed across human cancers, suggesting selection, or an active role for these alterations in follicular dendritic cell sarcoma pathogenesis. In support of a tumor suppressor-driven biology, homozygous deletions involving tumor suppressor genes
CDKN2A
,
RB1
,
BIRC3,
and
CYLD
were also observed. Neither recurrent gains nor amplifications were observed. This genomic characterization provides new information regarding follicular dendritic cell sarcoma biology that may improve understanding about the underlying pathophysiology, provide better prognostication, and identify potential therapeutic markers for this rare disease. |
| doi_str_mv | 10.1038/modpathol.2017.34 |
| format | Article |
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CDKN2A
,
RB1
,
BIRC3,
and
CYLD
were also observed. Neither recurrent gains nor amplifications were observed. This genomic characterization provides new information regarding follicular dendritic cell sarcoma biology that may improve understanding about the underlying pathophysiology, provide better prognostication, and identify potential therapeutic markers for this rare disease.</description><identifier>ISSN: 0893-3952</identifier><identifier>EISSN: 1530-0285</identifier><identifier>DOI: 10.1038/modpathol.2017.34</identifier><identifier>PMID: 28621320</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>45 ; 631/208/1405 ; 631/208/212/2301 ; 631/67/68 ; 692/420/2489/68 ; 692/699/67/1798 ; Adult ; Aged ; Biology ; Biomarkers, Tumor - genetics ; Chromosomes ; Chromosomes, Human ; Dendritic Cell Sarcoma, Follicular - genetics ; Dendritic Cell Sarcoma, Follicular - pathology ; Dendritic cells ; Female ; Formaldehyde ; Gene Deletion ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Genes, Tumor Suppressor ; Genetic Predisposition to Disease ; Genomic analysis ; Genomics - methods ; Homozygote ; Humans ; Inversion ; Laboratory Medicine ; Loss of Heterozygosity ; Male ; Medicine ; Medicine & Public Health ; Middle Aged ; Oligonucleotide Array Sequence Analysis ; original-article ; Paraffin ; Pathogenesis ; Pathology ; Pathophysiology ; Phenotype ; Rare diseases ; Sarcoma ; T cell receptors ; Tumor suppressor genes ; Young Adult</subject><ispartof>Modern pathology, 2017-09, Vol.30 (9), p.1321-1334</ispartof><rights>United States & Canadian Academy of Pathology USCAP, Inc 2017</rights><rights>Copyright Nature Publishing Group Sep 2017</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c481t-c1bc23d8d6d9126837c285e2b00b107a026efb3fc920a73a2d3483c890bd87a93</citedby><cites>FETCH-LOGICAL-c481t-c1bc23d8d6d9126837c285e2b00b107a026efb3fc920a73a2d3483c890bd87a93</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.proquest.com/docview/1934234963?pq-origsite=primo$$EHTML$$P50$$Gproquest$$H</linktohtml><link.rule.ids>314,777,781,27905,27906,64364,64368,72218</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28621320$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Andersen, Erica F</creatorcontrib><creatorcontrib>Paxton, Christian N</creatorcontrib><creatorcontrib>O'Malley, Dennis P</creatorcontrib><creatorcontrib>Louissaint Jr, Abner</creatorcontrib><creatorcontrib>Hornick, Jason L</creatorcontrib><creatorcontrib>Griffin, Gabriel K</creatorcontrib><creatorcontrib>Fedoriw, Yuri</creatorcontrib><creatorcontrib>Kim, Young S</creatorcontrib><creatorcontrib>Weiss, Lawrence M</creatorcontrib><creatorcontrib>Perkins, Sherrie L</creatorcontrib><creatorcontrib>South, Sarah T</creatorcontrib><title>Genomic analysis of follicular dendritic cell sarcoma by molecular inversion probe array reveals tumor suppressor-driven biology</title><title>Modern pathology</title><addtitle>Mod Pathol</addtitle><addtitle>Mod Pathol</addtitle><description>Follicular dendritic cell sarcoma is a rare malignant neoplasm of dendritic cell origin that is currently poorly characterized by genetic studies. To investigate whether recurrent genomic alterations may underlie the biology of follicular dendritic cell sarcoma and to identify potential contributory regions and genes, molecular inversion probe array analysis was performed on 14 independent formalin-fixed, paraffin-embedded samples. Abnormal genomic profiles were observed in 11 out of 14 (79%) cases. The majority showed extensive genomic complexity that was predominantly represented by hemizygous losses affecting multiple chromosomes. Alterations of chromosomal regions 1p (55%), 2p (55%), 3p (82%), 3q (45%), 6q (55%), 7q (73%), 8p (45%), 9p (64%), 11q (64%), 13q (91%), 14q (82%), 15q (64%), 17p (55%), 18q (64%), and 22q (55%) were recurrent across the 11 samples showing abnormal genomic profiles. Many recurrent genomic alterations in follicular dendritic cell sarcoma overlap deletions that are frequently observed across human cancers, suggesting selection, or an active role for these alterations in follicular dendritic cell sarcoma pathogenesis. In support of a tumor suppressor-driven biology, homozygous deletions involving tumor suppressor genes
CDKN2A
,
RB1
,
BIRC3,
and
CYLD
were also observed. Neither recurrent gains nor amplifications were observed. This genomic characterization provides new information regarding follicular dendritic cell sarcoma biology that may improve understanding about the underlying pathophysiology, provide better prognostication, and identify potential therapeutic markers for this rare disease.</description><subject>45</subject><subject>631/208/1405</subject><subject>631/208/212/2301</subject><subject>631/67/68</subject><subject>692/420/2489/68</subject><subject>692/699/67/1798</subject><subject>Adult</subject><subject>Aged</subject><subject>Biology</subject><subject>Biomarkers, Tumor - genetics</subject><subject>Chromosomes</subject><subject>Chromosomes, Human</subject><subject>Dendritic Cell Sarcoma, Follicular - genetics</subject><subject>Dendritic Cell Sarcoma, Follicular - pathology</subject><subject>Dendritic cells</subject><subject>Female</subject><subject>Formaldehyde</subject><subject>Gene Deletion</subject><subject>Gene Expression Profiling</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Genes, Tumor Suppressor</subject><subject>Genetic Predisposition to Disease</subject><subject>Genomic analysis</subject><subject>Genomics - methods</subject><subject>Homozygote</subject><subject>Humans</subject><subject>Inversion</subject><subject>Laboratory Medicine</subject><subject>Loss of Heterozygosity</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Middle Aged</subject><subject>Oligonucleotide Array Sequence Analysis</subject><subject>original-article</subject><subject>Paraffin</subject><subject>Pathogenesis</subject><subject>Pathology</subject><subject>Pathophysiology</subject><subject>Phenotype</subject><subject>Rare diseases</subject><subject>Sarcoma</subject><subject>T cell receptors</subject><subject>Tumor suppressor genes</subject><subject>Young 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inversion probe array reveals tumor suppressor-driven biology</title><author>Andersen, Erica F ; Paxton, Christian N ; O'Malley, Dennis P ; Louissaint Jr, Abner ; Hornick, Jason L ; Griffin, Gabriel K ; Fedoriw, Yuri ; Kim, Young S ; Weiss, Lawrence M ; Perkins, Sherrie L ; South, Sarah T</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c481t-c1bc23d8d6d9126837c285e2b00b107a026efb3fc920a73a2d3483c890bd87a93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>45</topic><topic>631/208/1405</topic><topic>631/208/212/2301</topic><topic>631/67/68</topic><topic>692/420/2489/68</topic><topic>692/699/67/1798</topic><topic>Adult</topic><topic>Aged</topic><topic>Biology</topic><topic>Biomarkers, Tumor - genetics</topic><topic>Chromosomes</topic><topic>Chromosomes, Human</topic><topic>Dendritic Cell Sarcoma, Follicular - genetics</topic><topic>Dendritic Cell Sarcoma, Follicular - pathology</topic><topic>Dendritic cells</topic><topic>Female</topic><topic>Formaldehyde</topic><topic>Gene Deletion</topic><topic>Gene Expression Profiling</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Genes, Tumor Suppressor</topic><topic>Genetic Predisposition to Disease</topic><topic>Genomic analysis</topic><topic>Genomics - methods</topic><topic>Homozygote</topic><topic>Humans</topic><topic>Inversion</topic><topic>Laboratory Medicine</topic><topic>Loss of Heterozygosity</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Middle Aged</topic><topic>Oligonucleotide Array Sequence Analysis</topic><topic>original-article</topic><topic>Paraffin</topic><topic>Pathogenesis</topic><topic>Pathology</topic><topic>Pathophysiology</topic><topic>Phenotype</topic><topic>Rare diseases</topic><topic>Sarcoma</topic><topic>T cell receptors</topic><topic>Tumor suppressor genes</topic><topic>Young 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China</collection><jtitle>Modern pathology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Andersen, Erica F</au><au>Paxton, Christian N</au><au>O'Malley, Dennis P</au><au>Louissaint Jr, Abner</au><au>Hornick, Jason L</au><au>Griffin, Gabriel K</au><au>Fedoriw, Yuri</au><au>Kim, Young S</au><au>Weiss, Lawrence M</au><au>Perkins, Sherrie L</au><au>South, Sarah T</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genomic analysis of follicular dendritic cell sarcoma by molecular inversion probe array reveals tumor suppressor-driven biology</atitle><jtitle>Modern pathology</jtitle><stitle>Mod Pathol</stitle><addtitle>Mod Pathol</addtitle><date>2017-09-01</date><risdate>2017</risdate><volume>30</volume><issue>9</issue><spage>1321</spage><epage>1334</epage><pages>1321-1334</pages><issn>0893-3952</issn><eissn>1530-0285</eissn><abstract>Follicular dendritic cell sarcoma is a rare malignant neoplasm of dendritic cell origin that is currently poorly characterized by genetic studies. To investigate whether recurrent genomic alterations may underlie the biology of follicular dendritic cell sarcoma and to identify potential contributory regions and genes, molecular inversion probe array analysis was performed on 14 independent formalin-fixed, paraffin-embedded samples. Abnormal genomic profiles were observed in 11 out of 14 (79%) cases. The majority showed extensive genomic complexity that was predominantly represented by hemizygous losses affecting multiple chromosomes. Alterations of chromosomal regions 1p (55%), 2p (55%), 3p (82%), 3q (45%), 6q (55%), 7q (73%), 8p (45%), 9p (64%), 11q (64%), 13q (91%), 14q (82%), 15q (64%), 17p (55%), 18q (64%), and 22q (55%) were recurrent across the 11 samples showing abnormal genomic profiles. Many recurrent genomic alterations in follicular dendritic cell sarcoma overlap deletions that are frequently observed across human cancers, suggesting selection, or an active role for these alterations in follicular dendritic cell sarcoma pathogenesis. In support of a tumor suppressor-driven biology, homozygous deletions involving tumor suppressor genes
CDKN2A
,
RB1
,
BIRC3,
and
CYLD
were also observed. Neither recurrent gains nor amplifications were observed. This genomic characterization provides new information regarding follicular dendritic cell sarcoma biology that may improve understanding about the underlying pathophysiology, provide better prognostication, and identify potential therapeutic markers for this rare disease.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>28621320</pmid><doi>10.1038/modpathol.2017.34</doi><tpages>14</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | 45 631/208/1405 631/208/212/2301 631/67/68 692/420/2489/68 692/699/67/1798 Adult Aged Biology Biomarkers, Tumor - genetics Chromosomes Chromosomes, Human Dendritic Cell Sarcoma, Follicular - genetics Dendritic Cell Sarcoma, Follicular - pathology Dendritic cells Female Formaldehyde Gene Deletion Gene Expression Profiling Gene Expression Regulation, Neoplastic Genes, Tumor Suppressor Genetic Predisposition to Disease Genomic analysis Genomics - methods Homozygote Humans Inversion Laboratory Medicine Loss of Heterozygosity Male Medicine Medicine & Public Health Middle Aged Oligonucleotide Array Sequence Analysis original-article Paraffin Pathogenesis Pathology Pathophysiology Phenotype Rare diseases Sarcoma T cell receptors Tumor suppressor genes Young Adult |
| title | Genomic analysis of follicular dendritic cell sarcoma by molecular inversion probe array reveals tumor suppressor-driven biology |
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