Fifty-five cases of t(14;18)2 follicular lymphoma (FL) were genetically characterized by targeted sequencing and copy number (CN) arrays. t(14;18)2 FL predominated in women (M/F 1:2); patients often presented during early clinical stages (71%), and had excellent prognoses. Overall, t(14;18)2 FL displayed CN alterations (CNAs) and gene mutations carried by conventional t(14;18)1 FL (cFL), but with different frequencies. The most frequently mutated gene was STAT6 (57%) followed by CREBBP (49%), TNFRSF14 (39%), and KMT2D (27%). t(14;18)2 FL showed significantly more STAT6 mutations and lacked MYD88, NOTCH2, MEF2B, and MAP2K1 mutations compared with cFL, nodal marginal zone lymphoma (NMZL), and pediatric-type FL (PTFL). We identified 2 molecular clusters. Cluster A was characterized by TNFRSF14 mutations/1p36 alterations (96%) and frequent mutations in epigenetic regulators, with recurrent loss of 6q21-24 sharing many features with cFL. Cluster B showed few genetic alterations; however, a subgroup with STAT6 mutations concurrent with CREBBP mutations/16p alterations without TNFRSF14 and EZH2 mutations was noted (65%). These 2 molecular clusters did not distinguish cases by inguinal localization, growth pattern, or presence of STAT6 mutations. BCL6 rearrangements were demonstrated in 10 of 45 (22%) cases and did not cluster together. Cases with predominantly inguinal presentation (20 of 50; 40%) had a higher frequency of diffuse growth pattern, STAT6 mutations, CD23 expression, and a lower number of CNAs, in comparison with noninguinal cases (5.1 vs 9.1 alterations per case; P,.05). STAT6 mutations showed a positive correlation with CD23 expression (P,.001). In summary, t(14;18)2 FL is genetically a heterogeneous disorder with features that differ from cFL, NMZL, and PTFL.

Nann, D., Ramis-Zaldivar, J.E., Muller, I., Gonzalez-Farre, B., Schmidt, J., Egan, C., et al. (2020). Follicular lymphoma t(14;18)-negative is genetically a heterogeneous disease. BLOOD ADVANCES, 4(22), 5652-5665 [10.1182/bloodadvances.2020002944].

Follicular lymphoma t(14;18)-negative is genetically a heterogeneous disease

Leoncini L.;
2020-01-01

Abstract

Fifty-five cases of t(14;18)2 follicular lymphoma (FL) were genetically characterized by targeted sequencing and copy number (CN) arrays. t(14;18)2 FL predominated in women (M/F 1:2); patients often presented during early clinical stages (71%), and had excellent prognoses. Overall, t(14;18)2 FL displayed CN alterations (CNAs) and gene mutations carried by conventional t(14;18)1 FL (cFL), but with different frequencies. The most frequently mutated gene was STAT6 (57%) followed by CREBBP (49%), TNFRSF14 (39%), and KMT2D (27%). t(14;18)2 FL showed significantly more STAT6 mutations and lacked MYD88, NOTCH2, MEF2B, and MAP2K1 mutations compared with cFL, nodal marginal zone lymphoma (NMZL), and pediatric-type FL (PTFL). We identified 2 molecular clusters. Cluster A was characterized by TNFRSF14 mutations/1p36 alterations (96%) and frequent mutations in epigenetic regulators, with recurrent loss of 6q21-24 sharing many features with cFL. Cluster B showed few genetic alterations; however, a subgroup with STAT6 mutations concurrent with CREBBP mutations/16p alterations without TNFRSF14 and EZH2 mutations was noted (65%). These 2 molecular clusters did not distinguish cases by inguinal localization, growth pattern, or presence of STAT6 mutations. BCL6 rearrangements were demonstrated in 10 of 45 (22%) cases and did not cluster together. Cases with predominantly inguinal presentation (20 of 50; 40%) had a higher frequency of diffuse growth pattern, STAT6 mutations, CD23 expression, and a lower number of CNAs, in comparison with noninguinal cases (5.1 vs 9.1 alterations per case; P,.05). STAT6 mutations showed a positive correlation with CD23 expression (P,.001). In summary, t(14;18)2 FL is genetically a heterogeneous disorder with features that differ from cFL, NMZL, and PTFL.
2020
Nann, D., Ramis-Zaldivar, J.E., Muller, I., Gonzalez-Farre, B., Schmidt, J., Egan, C., et al. (2020). Follicular lymphoma t(14;18)-negative is genetically a heterogeneous disease. BLOOD ADVANCES, 4(22), 5652-5665 [10.1182/bloodadvances.2020002944].
File in questo prodotto:
File Dimensione Formato  
Follicular lymphoma t(14;18)-negative-Nann-2020.pdf

non disponibili

Descrizione: Free full-text sul sito dell'editore
Tipologia: PDF editoriale
Licenza: NON PUBBLICO - Accesso privato/ristretto
Dimensione 2.97 MB
Formato Adobe PDF
2.97 MB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11365/1143213