Immunoglobulin gene rearrangement IGHV3-48 is a predictive marker of histological transformation into aggressive lymphoma in follicular lymphomas

• Published in: Blood cancer journal (New York) Vol. 9; no. 7; pp. 52 - 10
• Main Authors: García-Álvarez, María, Alonso-Álvarez, Sara, Prieto-Conde, Isabel, Jiménez, Cristina, Sarasquete, M. Eugenia, Chillón, M. Carmen, Medina, Alejandro, Balanzategui, Ana, Maldonado, Rebeca, Antón, Alicia, Puig, Noemí, Rodríguez, Marta, Blanco, Oscar, Tamayo, Pilar, González-Calle, Verónica, Martín, Alejandro, García-Sanz, Ramón, González, Marcos, Caballero, M. Dolores, Alcoceba, Miguel
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 17-06-2019; Springer Nature B.V
• Subjects: 45/23; 45/77; 631/67/1990/291/1621/1915; 692/499; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor - genetics; Biomedical and Life Sciences; Biomedicine; Cancer Research; Female; Gene Rearrangement, B-Lymphocyte, Heavy Chain; Genes; Genes, Immunoglobulin Heavy Chain; Hematology; Humans; Immunoglobulin Variable Region; Immunoglobulins; Lymphoma; Lymphoma, Follicular - genetics; Lymphoma, Follicular - immunology; Lymphoma, Follicular - pathology; Lymphoma, Large B-Cell, Diffuse - genetics; Lymphoma, Large B-Cell, Diffuse - immunology; Lymphoma, Large B-Cell, Diffuse - pathology; Male; Middle Aged; Oncology; Prognosis; Young Adult
• ISSN: 2044-5385; 2044-5385
• DOI: 10.1038/s41408-019-0213-9

Follicular lymphoma (FL) is a heterogeneous disease whose pathogenesis remains partially unknown. Around 20% of FL patients experience early progression or treatment-refractory disease and 2–3% of patients per year experience histological transformation (HT) into a more aggressive lymphoma (tFL). Here, we evaluate the immunoglobulin heavy chain variable (
IGHV
) gene usage and mutational status in 187 FL cases to assess its impact on clinical outcome and histological transformation. The
IGHV
gene repertoire was remarkably biased in FL. The
IGHV4-34
(14%),
IGHV3-23
(14%),
IGHV3-48
(10%),
IGHV3-30
(9%) and
IGHV3-21
(7%) genes accounted for more than half of the whole cohort.
IGHV3-48
was overrepresented in cases of tFL (19%) compared with non-transformed FL at 5 years (5%,
P
 = 0.05). Patients with the
IGHV3-48
gene were significantly more likely to have had HT after 10 years than those who used other genes (71% vs. 25%,
P
 < 0.05), irrespective of the therapy they received. Moreover,
IGHV3-30
was also overrepresented in cases of FL (9%) and tFL (13%) compared with diffuse large B-cell lymphoma in which it was nearly absent. In conclusion, our results indicate a role for antigen selection in the development of FL, while the use of
IGHV3-48
could help predict histological transformation.