Real‐life targeted next‐generation sequencing for lymphoma diagnosis over 1 year from the French Lymphoma Network

Abstract

Summary As the impact of targeted next‐generation sequencing (TNGS) on daily diagnosis has not been evaluated, we performed TNGS (46 genes) on lymphomas of unclear subtype following expert haematopathological review. The potential impact on patient care and modifications of final diagnosis were divided into major and minor changes according to the European Society of Medical Oncology (ESMO) guidelines. Among 229 patients [19 primary central nervous system lymphomas (PCNSL), 48 large B‐cell lymphomas (LBCLs), 89 small BCLs (SBCLs), seven Hodgkin lymphomas (HL), 66 T‐cell lymphomas], the overall concordance rate of histological and TNGS diagnosis was 89·5%. TNGS confirmed the histological diagnosis in 144 cases (62·9%), changed the diagnosis in 24 cases (10·5%) and did not help to clarify diagnosis in 61 cases (26·7%). Modifications to the final diagnosis had a clinical impact on patient care in 8·3% of cases. Diagnostic modifications occurred in all types of lymphoma except in PCNSL and HL; the modification rate was 14·6% in SBCL and 12·5% in LBCL. While comparing informative and uninformative cases, no differences were found in terms of DNA amplification, quality or depth of sequencing and biopsy type. The present study highlights that TNGS may directly contribute to a more accurate diagnosis in difficult‐to‐diagnose lymphomas, thus improving the clinical management in routine practice.

Deciphering the spectrum of cutaneous lymphomas expressing TFH markers

“…Concerning AITL, most studies concern nodal locations, in which mutations of TET2 (52-76%), IDH2 (20-45%), DNMT3A (30-40%) and RHOA G17V (28-70%) seem frequent [11][12][13][14][15][16] . The only study currently published in cutaneous localizations is the one of Leclaire Alirkilicarslan et al, which included 41 patients and found IDH2 R172K/S and RHOA G17V mutations in 19% and 78% of cases respectively using PCR 17 .…”

“…Leclaire Alirkilicarslan et al found 78% of RHOA G17V and 19% of cases with IDH2 R172 substitutions using www.nature.com/scientificreports/ PCR in a cohort of cAITL. In nodal AITL, mutations are much more frequent 11,12,15 ; TET2 SNV (76%), RHOA G17V (60-78%), and IDH2 R172 substitutions (19.5%). In the present study, the percentage of mutated cases was lower than described in the literature, and no IDH2 pathogenic variants were found.…”

“…TCR Clonality was assessed using the BIOMED-2 primer sets for TCR gamma (TCRG). TNGS have been performed as previously reported 11,23 . The applied panel of 47 genes is detailed in Suppl.…”

Next generation sequencing in routine diagnostics of maturenon‐Hodgkin's B‐cell lymphomas

“…These 10 cases were classified as MZL ( n = 7), LPL ( n = 2), and HCL‐v ( n = 1). Bommier et al 15 reported diagnostic impact in 73% (168/229 cases) of patient samples using a 46 custom‐made gene panel. The majority of these cases ( n = 144) were confirmatory of the diagnosis and there were no cases of unclassified to classified lymphoma.…”

“…However, characteristic mutational profiles in different types of lymphomas and probable prognostic algorithms based on mutational findings are being increasingly reported in the literature. [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18] Specific mutations may aid in diagnostic refinement and serve as inclusion or exclusion criteria to protocolled treatment strategies 19,20 as well as trial stratification.…”