Genomic signatures in B-cell lymphoma: How can these improve precision in diagnosis and inform prognosis?

Iqbal, Javeed; Naushad, Hina; Bi, Chengfeng; Yu, Jiayu; Bouska, Alyssa; Rohr, Joseph; Wang, Chao; Fu, Kai; Chan, Wing C.; Vose, Julie M.

doi:10.1016/j.blre.2015.08.002

Cited by 24 publications

(10 citation statements)

References 130 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…For example, the frequency of TP53 mutations was comparable, reaching 22.8% in MCL and 19.8% in DLBCL. These results match well with the recently published comprehensive data presenting 25% for MCL and 20 % for DLBCL (7). Similarly, the ratio of missense TP53 mutations was comparable for MCL and DLBCL reaching 76.9 and 82.8%, respectively.…”

Section: Discussionsupporting

confidence: 92%

“…Recently, the data have been reviewed and summarized for DLBCL, follicular lymphoma (FL), Burkitt lymphoma (BL), mantle cell lymphoma (MCL), marginal zone B-cell lymphoma (MZBL) and primary mediastinal B-cell lymphoma (PMBL). Acquisition of TP53 mutation was demonstrated as one of characteristic markers for DLBCL and MCL, reaching frequency 20 and 25%, respectively, but not for other lymphomas (7). This supports the concept of alternative ways abrogating the p53-dependent apoptosis.…”

Section: Complex Analysis Of the Tp53 Tumor Suppressor In Mantle Cellsupporting

confidence: 52%

See 1 more Smart Citation

Complex analysis of the TP53 tumor suppressor in mantle cell and diffuse large B-cell lymphomas

et al. 2017

View full text Add to dashboard Cite

Mutations and deletions of the tumor suppressor TP53 gene are the most frequent genetic alterations detected in human tumors, though they are rather less frequent in lymphomas. However, acquisition of the TP53 mutation was demonstrated to be one of the characteristic markers in mantle cell lymphoma (MCL) and diffuse large B-cell lymphoma (DLBCL) and prognostic value of the TP53 status has been recognized for these diseases. We present the complex analysis of the TP53 aberrations in 57 cases of MCL and 131 cases of DLBCL. The TP53 status was determined by functional analyses in yeast (FASAY) followed by cDNA and gDNA sequencing. The level of the p53 protein was assessed by immunoblotting and loss of the TP53-specific locus 17p13.3 was detected by FISH. Altogether, we detected 13 TP53 mutations among MCL cases (22.8%) and 29 TP53 mutations in 26 from 131 DLBCL cases (19.8%). The ratio of missense TP53 mutations was 76.9% in MCL and 82.8% in DLBCL. The frequency of TP53 locus deletion was rather low in both diseases, reaching 9.3% in MCL and 15.3% in DLBCL. The presence of TP53 mutation was associated with shorter overall survival (OS) and progression-free survival (PFS) in MCL. Among DLBCL cases, the TP53 mutations shortened both OS and PFS of patients treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) and decreased both OS and PFS of patients with secondary DLBCL disease.

show abstract

Section: Discussionsupporting

confidence: 92%

Section: Complex Analysis Of the Tp53 Tumor Suppressor In Mantle Cellsupporting

confidence: 52%

Complex analysis of the TP53 tumor suppressor in mantle cell and diffuse large B-cell lymphomas

et al. 2017

View full text Add to dashboard Cite

show abstract

“…CREBBP , KMT2D (previously termed MLL2 ), BCL2 , EZH2 , and TP53 ] and T‐lineage (e.g. TET2 , LRRK2 , PCLO , SPEN ) lymphomas, as seen in de novo diseases (Iqbal et al , , ). Consistent with this observation, mutation burden was higher in B‐cell versus T‐cell lymphomas.…”

Section: Resultsmentioning

confidence: 99%

Phase I/II study of dasatinib and exploratory genomic analysis in relapsed or refractory non‐Hodgkin lymphoma

et al. 2018

Self Cite

View full text Add to dashboard Cite

Summary Relapsed or refractory non‐Hodgkin lymphomas (NHLs) often carry poor prognosis and pose management challenges. We evaluated the safety and efficacy of dasatinib, a broad‐spectrum multi‐kinase inhibitor in relapsed/refractory NHL with correlative genomic analysis in a Phase I/II trial. The study included 33 patients with various sub‐types of NHL who had received at least one prior therapy. The most common sub‐types were diffuse large B‐cell lymphoma (24%), follicular lymphoma, grade 1/2 (21%) and peripheral T‐cell lymphoma not otherwise specified (PTCL‐NOS; 21%). Most patients were heavily pre‐treated, including 42% with more than four prior therapies, 67% with rituximab exposure and 24% with prior autologous transplant. In this cohort, dasatinib showed modest activity in evaluable patients with an objective response rate of 29% (7/24) and clinical benefit rate of 71% (17/24). In 32 patients with outcome data, median progression‐free survival was 3 months and median overall survival was 22·4 months. There were two patients with sustained complete responses, both with PTCL‐NOS histology. The side effect profile was consistent with prior studies, with pleural effusion being the most common non‐haematological toxicity. Exploratory genomic analysis showed two cases of PTCL‐NOS with sustained response had a common mutation in LRRK2 and high prevalence of FOXO1 mutation in relapsed/refractory follicular lymphoma.

show abstract

“…definition, patients may develop accompanying B-cell lymphoproliferative disorders or clonal plasma cell proliferations as reported previously. 7,8 Importantly, recent studies have shown that AITL has a gene expression profile similar to that of follicular helper T (T FH ) cells, 2,9,10 a subset of T helper cells in the germinal center that promotes B-cell maturation and differentiation into plasma cells in cooperation with FDCs. Accordingly, in addition to expressing pan-T-cell antigens such as CD3 and CD5, the neoplastic cells of AITL usually express T FH markers such as CD10, BCL6, and/or PD-1.…”

mentioning

confidence: 99%

Cutaneous lesions of angioimmunoblastic T‐cell lymphoma: Clinical, pathological, and immunophenotypic features

et al. 2019

View full text Add to dashboard Cite

Background Angioimmunoblastic T‐cell lymphoma (AITL) is a systemic peripheral T‐cell lymphoma with a follicular helper T‐cell (TFH) immunophenotype that frequently involves the skin. However, the histopathology of cutaneous involvement by AITL has not been fully established. Methods We reviewed the clinicopathological features of 19 patients seen at our institution with AITL involving the skin. Pan‐T‐cell and TFH marker expression was evaluated by immunohistochemistry. Epstein‐Barr virus (EBV) was detected using in situ hybridization (ISH) for Epstein‐Barr virus‐encoded small RNA (EBER). T‐cell receptor (TCR) gene rearrangement was evaluated by PCR. Results AITL affected both trunk and extremities in 15/19 cases (79%). Perivascular infiltration by small and/or medium‐sized lymphocytes was seen in 18/19 (95%). Granulomatous inflammation was identified in 4/19 (21%). Aberrant loss of CD2, CD5, or CD7 was identified in 1/18 (6%), 2/18 (11%), or 7/19 (37%) cases, respectively. Seventeen of eighteen evaluable cases (95%) expressed 2 to 3 TFH markers: PD‐1 in 19/19 (100%), BCL6 in 94% (17/18), and CD10 in 37% (7/19). EBV‐positive cells were detected in 3/18 (17%) with varying density. Clonal TCR gene rearrangement was identified in 9/11 (82%). Conclusions Cutaneous involvement by AITL shows relatively non‐specific histopathological features. However, an immunohistochemical panel including TFH markers and EBER ISH is useful in differential diagnosis.

show abstract

Genomic signatures in B-cell lymphoma: How can these improve precision in diagnosis and inform prognosis?

Cited by 24 publications

References 130 publications

Complex analysis of the TP53 tumor suppressor in mantle cell and diffuse large B-cell lymphomas

Complex analysis of the TP53 tumor suppressor in mantle cell and diffuse large B-cell lymphomas

Phase I/II study of dasatinib and exploratory genomic analysis in relapsed or refractory non‐Hodgkin lymphoma

Cutaneous lesions of angioimmunoblastic T‐cell lymphoma: Clinical, pathological, and immunophenotypic features

Contact Info

Product

Resources

About