An Immunogenetic Signature of Ongoing Antigen Interactions in
Splenic Marginal Zone Lymphoma Expressing IGHV1-2*04 Receptors

J 2016

An Immunogenetic Signature of Ongoing Antigen Interactions in Splenic Marginal Zone Lymphoma Expressing IGHV1-2*04 Receptors

BIKOS, Vasileios, Maria KARYPIDOU, Evangelia STALIKA, Panagiotis BALIAKAS, Aliki XOCHELLI et. al.

Basic information

Original name

An Immunogenetic Signature of Ongoing Antigen Interactions in Splenic Marginal Zone Lymphoma Expressing IGHV1-2*04 Receptors

Name in Czech

Imunogenetické Podpis probíhajících interakcí antigenu v marginální zóně sleziny lymfomem Vyjádření IGHV1-2 * 04 receptory

Authors

BIKOS, Vasileios (300 Greece, belonging to the institution), Maria KARYPIDOU (300 Greece), Evangelia STALIKA (300 Greece), Panagiotis BALIAKAS (300 Greece), Aliki XOCHELLI (300 Greece), Lesley-Ann SUTTON (752 Sweden), George PAPADOPOULOS (300 Greece), Andreas AGATHANGELIDIS (380 Italy), Evdoxia PAPADOPOULOU (300 Greece), Zadie DAVIS (826 United Kingdom of Great Britain and Northern Ireland), Patricia ALGARA (724 Spain), George KANELLIS (300 Greece), Alexandra TRAVERSE-GLEHEN (250 France), Manuela MOLLEJO (724 Spain), Achilles ANAGNOSTOPOULOS (300 Greece), Maurilio PONZONI (380 Italy), David GONZALEZ (826 United Kingdom of Great Britain and Northern Ireland), Šárka POSPÍŠILOVÁ (203 Czech Republic, guarantor, belonging to the institution), Estella MATUTES (826 United Kingdom of Great Britain and Northern Ireland), Miguel Angel PIRIS (724 Spain), Theodora PAPADAKI (300 Greece), Paolo GHIA (380 Italy), Richard ROSENQUIST (752 Sweden), David OSCIER (826 United Kingdom of Great Britain and Northern Ireland), Nikos DARZENTAS (300 Greece, belonging to the institution), Dimitros TZOVARAS (300 Greece), Chrysoula BELESSI (752 Sweden), Anastasia HADZIDIMITRIOU (300 Greece) and Kostas STAMATOPOULOS (300 Greece)

Edition

Clinical cancer research, Philadelphia, AMER ASSOC CANCER RESEARCH, 2016, 1078-0432

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30200 3.2 Clinical medicine

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 9.619

RIV identification code

RIV/00216224:14740/16:00092191

Organization unit

Central European Institute of Technology

DOI

http://dx.doi.org/10.1158/1078-0432.CCR-15-1170

UT WoS

000374101400024

Keywords in English

HRONIC LYMPHOCYTIC-LEUKEMIA; SOMATIC HYPERMUTATION; V-H; IMMUNOGLOBULIN GENES; DATA-COMPRESSION; CELL-RECEPTOR; LIGHT-CHAIN; SEQUENCE; MUTATION; ANTIBODIES

Abstract

ORIG CZ

V originále

Purpose: Prompted by the extensive biases in the immunoglobulin (IG) gene repertoire of splenic marginal-zone lymphoma (SMZL), supporting antigen selection in SMZL ontogeny, we sought to investigate whether antigen involvement is also relevant post-transformation. Experimental Design: We conducted a large-scale subcloning study of the IG rearrangements of 40 SMZL cases aimed at assessing intraclonal diversification (ID) due to ongoing somatic hypermutation (SHM). Results: ID was identified in 17 of 21 (81%) rearrangements using the immunoglobulin heavy variable (IGHV) 1-2*04 gene versus 8 of 19 (40%) rearrangements utilizing other IGHV genes (P = 0.001). ID was also evident in most analyzed IG light chain gene rearrangements, albeit was more limited compared with IG heavy chains. Identical sequence changes were shared by subclones from different patients utilizing the IGHV1-2*04 gene, confirming restricted ongoing SHM profiles. Non-IGHV1-2*04 cases displayed both a lower number of ongoing SHMs and a lack of shared mutations (per group of cases utilizing the same IGHV gene). Conclusions: These findings support ongoing antigen involvement in a sizable portion of SMZL and further argue that IGHV1-2*04 SMZL may represent a distinct molecular subtype of the disease. (C) 2015 AACR.

In Czech

Účel: vyzvání rozsáhlých chyb ve genu repertoáru imunoglobulinu (IG) ze sleziny marginální zóny lymfomu (SMZL), podporující výběr antigenu v SMZL ontogeneze jsme se snažili zjistit, zda zapojení antigen je rovněž relevantní post-transformace. Experimentální design: My vzhledem k probíhajícímu somatické hypermutation (SHM) provedla rozsáhlou studii o klonování IG přeskupení 40 případů SMZL s cílem posoudit intraclonal diverzifikaci (ID). Výsledky: ID byl zjištěn u 17 z 21 (81%) přeskupení použitím imunoglobulinového těžkého proměnnou (IGHV) 1-2 * 04 gen oproti 8 z 19 (40%) s využitím dalších přestaveb IGHV geny (p = 0,001). ID byl patrný ve většině analyzovaných genů přestaveb Ig lehkého řetězce, i když byl omezenější ve srovnání s Ig těžkého řetězce. Identické sekvenční změny byly sdíleny subklonů z různých pacientů využívajících gen IGHV1-2 * 04, což potvrzuje omezený probíhající SHM profily. Non-IGHV1-2 * 04 případů zobrazena jak nižší počet probíhající SHMS a nedostatek společných mutací (za skupinu případů využívajících stejný IGHV gen). Závěr: Tato zjištění podporují pokračující zapojení antigenu ve značné části SMZL a dále tvrdí, že IGHV1-2 * 04 SMZL může představovat zřetelnou molekulovou podtyp onemocnění. (C) 2015 AACR.

Links

ED1.1.00/02.0068, research and development project

Name: CEITEC - central european institute of technology

EE2.3.20.0045, research and development project

Name: Podpora profesního růstu a mezinárodní integrace výzkumných týmů v oblasti molekulární medicíny

Citovat

BIKOS, Vasileios, Maria KARYPIDOU, Evangelia STALIKA, Panagiotis BALIAKAS, Aliki XOCHELLI, Lesley-Ann SUTTON, George PAPADOPOULOS, Andreas AGATHANGELIDIS, Evdoxia PAPADOPOULOU, Zadie DAVIS, Patricia ALGARA, George KANELLIS, Alexandra TRAVERSE-GLEHEN, Manuela MOLLEJO, Achilles ANAGNOSTOPOULOS, Maurilio PONZONI, David GONZALEZ, Šárka POSPÍŠILOVÁ, Estella MATUTES, Miguel Angel PIRIS, Theodora PAPADAKI, Paolo GHIA, Richard ROSENQUIST, David OSCIER, Nikos DARZENTAS, Dimitros TZOVARAS, Chrysoula BELESSI, Anastasia HADZIDIMITRIOU and Kostas STAMATOPOULOS. An Immunogenetic Signature of Ongoing Antigen Interactions in Splenic Marginal Zone Lymphoma Expressing IGHV1-2*04 Receptors. Clinical cancer research. Philadelphia: AMER ASSOC CANCER RESEARCH, 2016, vol. 22, No 8, p. 2032-2040. ISSN 1078-0432. Available from: https://dx.doi.org/10.1158/1078-0432.CCR-15-1170.

@article{1363889,
   author = {Bikos, Vasileios and Karypidou, Maria and Stalika, Evangelia and Baliakas, Panagiotis and Xochelli, Aliki and Sutton, LesleyandAnn and Papadopoulos, George and Agathangelidis, Andreas and Papadopoulou, Evdoxia and Davis, Zadie and Algara, Patricia and Kanellis, George and TraverseandGlehen, Alexandra and Mollejo, Manuela and Anagnostopoulos, Achilles and Ponzoni, Maurilio and Gonzalez, David and Pospíšilová, Šárka and Matutes, Estella and Piris, Miguel Angel and Papadaki, Theodora and Ghia, Paolo and Rosenquist, Richard and Oscier, David and Darzentas, Nikos and Tzovaras, Dimitros and Belessi, Chrysoula and Hadzidimitriou, Anastasia and Stamatopoulos, Kostas},
   article_location = {Philadelphia},
   article_number = {8},
   doi = {http://dx.doi.org/10.1158/1078-0432.CCR-15-1170},
   keywords = {HRONIC LYMPHOCYTIC-LEUKEMIA; SOMATIC HYPERMUTATION; V-H; IMMUNOGLOBULIN GENES; DATA-COMPRESSION; CELL-RECEPTOR; LIGHT-CHAIN; SEQUENCE; MUTATION; ANTIBODIES},
   language = {eng},
   issn = {1078-0432},
   journal = {Clinical cancer research},
   title = {An Immunogenetic Signature of Ongoing Antigen Interactions in Splenic Marginal Zone Lymphoma Expressing IGHV1-2*04 Receptors},
   url = {http://clincancerres.aacrjournals.org/content/22/8/2032},
   volume = {22},
   year = {2016}
}

TY  - JOUR
ID  - 1363889
AU  - Bikos, Vasileios - Karypidou, Maria - Stalika, Evangelia - Baliakas, Panagiotis - Xochelli, Aliki - Sutton, Lesley-Ann - Papadopoulos, George - Agathangelidis, Andreas - Papadopoulou, Evdoxia - Davis, Zadie - Algara, Patricia - Kanellis, George - Traverse-Glehen, Alexandra - Mollejo, Manuela - Anagnostopoulos, Achilles - Ponzoni, Maurilio - Gonzalez, David - Pospíšilová, Šárka - Matutes, Estella - Piris, Miguel Angel - Papadaki, Theodora - Ghia, Paolo - Rosenquist, Richard - Oscier, David - Darzentas, Nikos - Tzovaras, Dimitros - Belessi, Chrysoula - Hadzidimitriou, Anastasia - Stamatopoulos, Kostas
PY  - 2016
TI  - An Immunogenetic Signature of Ongoing Antigen Interactions in Splenic Marginal Zone Lymphoma Expressing IGHV1-2*04 Receptors
JF  - Clinical cancer research
VL  - 22
IS  - 8
SP  - 2032-2040
EP  - 2032-2040
PB  - AMER ASSOC CANCER RESEARCH
SN  - 10780432
KW  - HRONIC LYMPHOCYTIC-LEUKEMIA
KW  - SOMATIC HYPERMUTATION
KW  - V-H
KW  - IMMUNOGLOBULIN GENES
KW  - DATA-COMPRESSION
KW  - CELL-RECEPTOR
KW  - LIGHT-CHAIN
KW  - SEQUENCE
KW  - MUTATION
KW  - ANTIBODIES
UR  - http://clincancerres.aacrjournals.org/content/22/8/2032
L2  - http://clincancerres.aacrjournals.org/content/22/8/2032
N2  - Purpose: Prompted by the extensive biases in the immunoglobulin (IG) gene repertoire of splenic marginal-zone lymphoma (SMZL), supporting antigen selection in SMZL ontogeny, we sought to investigate whether antigen involvement is also relevant post-transformation. Experimental Design: We conducted a large-scale subcloning study of the IG rearrangements of 40 SMZL cases aimed at assessing intraclonal diversification (ID) due to ongoing somatic hypermutation (SHM). Results: ID was identified in 17 of 21 (81%) rearrangements using the immunoglobulin heavy variable (IGHV) 1-2*04 gene versus 8 of 19 (40%) rearrangements utilizing other IGHV genes (P = 0.001). ID was also evident in most analyzed IG light chain gene rearrangements, albeit was more limited compared with IG heavy chains. Identical sequence changes were shared by subclones from different patients utilizing the IGHV1-2*04 gene, confirming restricted ongoing SHM profiles. Non-IGHV1-2*04 cases displayed both a lower number of ongoing SHMs and a lack of shared mutations (per group of cases utilizing the same IGHV gene). Conclusions: These findings support ongoing antigen involvement in a sizable portion of SMZL and further argue that IGHV1-2*04 SMZL may represent a distinct molecular subtype of the disease. (C) 2015 AACR.
ER  -

BIKOS, Vasileios, Maria KARYPIDOU, Evangelia STALIKA, Panagiotis BALIAKAS, Aliki XOCHELLI, Lesley-Ann SUTTON, George PAPADOPOULOS, Andreas AGATHANGELIDIS, Evdoxia PAPADOPOULOU, Zadie DAVIS, Patricia ALGARA, George KANELLIS, Alexandra TRAVERSE-GLEHEN, Manuela MOLLEJO, Achilles ANAGNOSTOPOULOS, Maurilio PONZONI, David GONZALEZ, Šárka POSPÍŠILOVÁ, Estella MATUTES, Miguel Angel PIRIS, Theodora PAPADAKI, Paolo GHIA, Richard ROSENQUIST, David OSCIER, Nikos DARZENTAS, Dimitros TZOVARAS, Chrysoula BELESSI, Anastasia HADZIDIMITRIOU and Kostas STAMATOPOULOS. An Immunogenetic Signature of Ongoing Antigen Interactions in Splenic Marginal Zone Lymphoma Expressing IGHV1-2*04 Receptors. \textit{Clinical cancer research}. Philadelphia: AMER ASSOC CANCER RESEARCH, 2016, vol.~22, No~8, p.~2032-2040. ISSN~1078-0432. Available from: https://dx.doi.org/10.1158/1078-0432.CCR-15-1170.

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