Immunoglobulin heavy variable (IGHV) genes and alleles: new entities, new names and implications for research and prognostication in chronic lymphocytic leukaemia

XOCHELLI, Aliki, Andreas AGATHANGELIDIS, Ioannis KAVAKIOTIS, Evangelia MINGA, Lesley Ann SUTTON, Panagiotis BALIAKAS, Ioanna CHOUVARDA, Veronique GIUDICELLI, Ioannis VLAHAVAS, Nikos MAGLAVERAS, Lisa BONELLO, Livio TRENTIN, Alessandra TEDESCHI, Panagiotis PANAGIOTIDIS, Christian GEISLER, Anton W. LANGERAK, Šárka POSPÍŠILOVÁ, Diane F. JELINEK, David OSCIER, Nicholas CHIORAZZI, Nikos DARZENTAS, Fred DAVI, Paolo GHIA, Richard ROSENQUIST, Anastasia HADZIDIMITRIOU, Chrysoula BELESSI, Marie-Paule LEFRANC and Kostas STAMATOPOULOS. Immunoglobulin heavy variable (IGHV) genes and alleles: new entities, new names and implications for research and prognostication in chronic lymphocytic leukaemia. Immunogenetics. New York: Springer, 2015, vol. 67, No 1, p. 61-66. ISSN 0093-7711. doi:10.1007/s00251-014-0812-3.

Basic information

• Original name: Immunoglobulin heavy variable (IGHV) genes and alleles: new entities, new names and implications for research and prognostication in chronic lymphocytic leukaemia
• Authors: XOCHELLI, Aliki (300 Greece), Andreas AGATHANGELIDIS (380 Italy), Ioannis KAVAKIOTIS (300 Greece), Evangelia MINGA (300 Greece), Lesley Ann SUTTON (752 Sweden), Panagiotis BALIAKAS (752 Sweden), Ioanna CHOUVARDA (300 Greece), Veronique GIUDICELLI (250 France), Ioannis VLAHAVAS (300 Greece), Nikos MAGLAVERAS (300 Greece), Lisa BONELLO (380 Italy), Livio TRENTIN (380 Italy), Alessandra TEDESCHI (380 Italy), Panagiotis PANAGIOTIDIS (300 Greece), Christian GEISLER (208 Denmark), Anton W. LANGERAK (528 Netherlands), Šárka POSPÍŠILOVÁ (203 Czech Republic, guarantor, belonging to the institution), Diane F. JELINEK (840 United States of America), David OSCIER (826 United Kingdom of Great Britain and Northern Ireland), Nicholas CHIORAZZI (840 United States of America), Nikos DARZENTAS (300 Greece, belonging to the institution), Fred DAVI (250 France), Paolo GHIA (380 Italy), Richard ROSENQUIST (752 Sweden), Anastasia HADZIDIMITRIOU (300 Greece), Chrysoula BELESSI (300 Greece), Marie-Paule LEFRANC (250 France) and Kostas STAMATOPOULOS (300 Greece).
• Edition: Immunogenetics, New York, Springer, 2015, 0093-7711.

Other information

• Original language: English
• Type of outcome: Article in a journal
• Field of Study: 30200 3.2 Clinical medicine
• Country of publisher: United States of America
• Confidentiality degree: is not subject to a state or trade secret
• WWW: URL
• Impact factor: Impact factor: 2.303
• RIV identification code: RIV/00216224:14740/15:00082537
• Organization unit: Central European Institute of Technology
• Doi: http://dx.doi.org/10.1007/s00251-014-0812-3
• UT WoS: 000347161000007
• Keywords in English: CLL; SHM; New IGHV genes; New IGHV gene alleles; Prognostication
• Tags: podil, rivok
• Tags: International impact, Reviewed

Abstract

Ieext generation sequencing studies in Homo sapiens have identified novel immunoglobulin heavy variable (IGHV) genes and alleles necessitating changes in the international ImMunoGeneTics information system (IMGT) GENE-DB and reference directories of IMGT/V-QUEST. In chronic lymphocytic leukaemia (CLL), the somatic hypermutation (SHM) status of the clonotypic rearranged IGHV gene is strongly associated with patient outcome. Correct determination of this parameter strictly depends on the comparison of the nucleotide sequence of the clonotypic rearranged IGHV gene with that of the closest germline counterpart. Consequently, changes in the reference directories could, in principle, affect the correct interpretation of the IGHV mutational status in CLL. To this end, we analyzed 8066 productive IG heavy chain (IGH) rearrangement sequences from our consortium both before and after the latest update of the IMGT/V-QUEST reference directory. Differences were identified in 405 cases (5 % of the cohort). In 291/405 sequences (71.9 %), changes concerned only the IGHV gene or allele name, whereas a change in the percent germline identity (%GI) was noted in 114/405 (28.1 %) sequences; in 50/114 (43.8 %) sequences, changes in the %GI led to a change in the mutational set. In conclusion, recent changes in the IMGT reference directories affected the interpretation of SHM in a sizeable number of IGH rearrangement sequences from CLL patients. This indicates that both physicians and researchers should consider a re-evaluation of IG sequence data, especially for those IGH rearrangement sequences that, up to date, have a GI close to 98 %, where caution is warranted.

Links

• ED1.1.00/02.0068, research and development project: Name: CEITEC - central european institute of technology
• NT13493, research and development project: Name: Molekulární charakterizace B buněčných receptorů a jejich vztah k evoluci genetických změn u chronické lymfocytární leukémie