Colorectal diffuse large B-cell lymphoma: molecular subclassification and prognostic significance of immunoglobulin gene translocation

Hori, Yozo; Yamamoto, Hidetaka; Torisu, Takehiro; Fujiwara, Minako; Taguchi, Kenichi; Nishiyama, Kenichi; Nakamura, Shotaro; Kitazono, Takanari

doi:10.1016/j.humpath.2019.09.003

Cited by 13 publications

(13 citation statements)

References 34 publications

(69 reference statements)

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“…The driver genes responsible for the development of gastrointestinal DLBCL differed from those of nodal or non-gastrointestinal DLBCL (27). First, TP53 mutations demonstrated a significantly increased mutation frequency compared with that in nodal DLBCL in COSMIC and common DLBCL in cBioPortal.…”

Section: Discussionmentioning

confidence: 99%

Genomic Mutation Profile of Primary Gastrointestinal Diffuse Large B-Cell Lymphoma

Chai

Chen

et al. 2021

Front. Oncol.

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Primary gastrointestinal diffuse large B-cell lymphoma (GI-DLBCL) is the most common gastrointestinal lymphoma, but its genetic features are poorly understood. We performed whole-exome sequencing of 25 primary tumor samples from patients with GI-DLBCL and 23 matched normal tissue samples. Oncogenic mutations were screened, and the correlations between genetic mutations and clinicopathological characteristics were analyzed. Twenty-five patients with GI-DLBCL were enrolled in the genetic mutation analysis with a median of 184 (range 79–382) protein-altering variants per patient. We identified recurrent oncogenic mutations in GI-DLBCL, including those in TP53, MUC16, B2M, CCND3, HIST1H1C, NEB, and ID3. Compared with nodal DLBCL, GI-DLBCL exhibited an increased mutation frequency of TP53 and reduced mutation frequencies of PIM1, CREBBP, BCL2, KMT2D, and EZH2. Moreover, GI-DLBCL exhibited fewer MYD88 and CD79B mutations than DLBCL in the testis and central nervous system. GI-DLBCLs with HLA-B, MEF2A, RHOA, and NAV3 mutations exhibited a tendency toward a high proliferation index. MUC16 and ETV6 mutations often occurred in tumors with early clinical staging. Our data provide a comprehensive understanding of the landscape of mutations in a small subset of GI-DLBCLs. The genetic mutation profiles of GI-DLBCL differ from those of nodal DLBCL and DLBCL in immune-privileged sites. The different mutated genes are related to the NF-κB and JAK-STAT pathways, and the different pathogenetic mechanisms leading to the development of DLBCL may be influenced by the tissue microenvironment. Differences in genetic alterations might influence the clinicopathological characteristics of GI-DLBCL.

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Section: Discussionmentioning

confidence: 99%

Genomic Mutation Profile of Primary Gastrointestinal Diffuse Large B-Cell Lymphoma

Chai

Chen

et al. 2021

Front. Oncol.

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“…IHC interpretation was performed by hematopathologists or other pathologists nearly three-quarters of the time (30/41, 73.2%). In brief, the study design was prospective in one study [59], retrospective in 22 [3,32,33,36,[38][39][40]42,[44][45][46][47][49][50][51]54,60,61,63,66,67,69], secondary analysis of primary clinical trials in six [37,41,48,53,57,58], and not-explained in 12 [19][20][21]34,35,43,52,55,56,62,65,68]. The number of patients per study ranged from 20 to 688, with median ages of 46-70 years.…”

Section: Characteristics Of the Included Studiesmentioning

confidence: 99%

“…The number of patients per study ranged from 20 to 688, with median ages of 46-70 years. Regarding cutoff values for MYC and BCL2 protein expression, 21 studies used >40% and >50% [20,[33][34][35]38,39,[41][42][43][44][45]47,49,[56][57][58]60,[62][63][64]69], 10 studies used >40% and >70% [3,19,48,50,51,53,54,[66][67][68], and two studies used >30% and >30% [55,65]. Six studies used other various criteria to define MYC and BCL2 protein expression [21,36,40,46,52,61].…”

Section: Characteristics Of the Included Studiesmentioning

confidence: 99%

The Incidence and Treatment Response of Double Expression of MYC and BCL2 in Patients with Diffuse Large B-Cell Lymphoma: A Systematic Review and Meta-Analysis

Hwang

Suh

Kim

et al. 2021

Cancers

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MYC/BCL2 protein co-expression (i.e., double expressor) has been shown to be a negative predictor of outcome in diffuse large B-cell lymphoma (DLBCL). We aimed to establish the incidence of double expressor status in patients with de novo DLBCL and identify the predictive value of this biomarker on treatment response through systematic review and meta-analysis. PubMed and Embase were searched for studies published through December 2019 that reported proportions of double expressor DLBCL. The pooled proportions of MYC and BCL2 expression, both alone and in combination, were computed using the inverse variance method for calculating weights and by the DerSimonian–Laird method. The pooled odds ratios (ORs) of complete remission (CR) rate were calculated, and meta-regression analysis was conducted to explore heterogeneity. Forty-one studies (7054 patients) were included. The pooled incidence of double expressor status in DLBCL was 23% (95% confidence interval [CI], 20–26%), with an adjusted estimate of 31% (95% CI, 27–36%). Neither MYC/BCL2 protein cutoff values, race, mean, or median age of included patients, or overall study quality was a significant factor of heterogeneity (p ≥ 0.20). Cases without double expressor status demonstrated a higher probability of CR to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone treatment (OR, 2.69; 95% CI, 1.55–4.67). Our results reaffirm the predictive power of this important biomarker.

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“…Adult T-cell leukemia/lymphoma (ATLL) consists of CD4+ T-cell neoplasm and frequently presents leukemic changes and tumor cell invasion in various organs, including the GI tract [13,14]. Primary colorectal B-cell lymphoma is found mainly in the ileocecum and endoscopically shows predominantly ulcerative and polypoid types, while diffuse infiltrating type is rare [15]. Small and large intestinal TNKCL including colorectal MEITL and EBV+ TNKCL often presents ulcero-infiltrative, ulcerating, and ulcerofungating type lesions [16].…”

Section: Introductionmentioning

confidence: 99%

Endoscopic and clinicopathological characteristics of colorectal T/NK cell lymphoma

et al. 2020

Self Cite

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Background Colorectal T/natural killer (NK)-cell lymphomas (TNKCL) are very rare. Endoscopic and clinicopathological characteristics of colorectal TNKCL have not been clearly demonstrated. In this study, we demonstrated the clinical characteristics of colorectal TNKCL. Methods Endoscopic and clinicopathological characteristics were investigated in 27 patients with colorectal monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL), adult T-cell leukemia/lymphoma (ATLL), and other types of TNKCL. Results Nine TNKCL patients (33%) were classified as MEITL, 11 (41%) as ATLL, and seven (26%) as other. Four patients with Epstein-Barr Virus-positive (EBV+) TNKCL, two indolent T-cell lymphoproliferative disorder and one anaplastic large cell lymphoma were included in the other group. Endoscopically, six MEITL (67%) and five ATLL (46%) showed diffuse-infiltrating type, in which the main endoscopic lesion was edematous mucosa in MEITL, while aphthoid erosion and edematous mucosa were typical in ATLL. Ulcerative type was identified in four other group patients (57%), including two EBV+ TNKCL. An increase in atypical T-intraepithelial lymphocytes (T-IELs) was noted in seven MEITL (88%) and six ATLL (60%) patients, but not in the other group (0%) patients. Five MEITL patients (56%) showed features of lymphocytic proctocolitis with increased CD8+ T-IELs. Conclusions MEITL and ATLL occasionally invaded the colorectum, and primary involving MEITL was observed. Diffuse infiltrating type was the characteristic endoscopic finding in colorectal MEITL and ATLL, while ulcerative type was observed in the other group. Features of lymphocytic proctocolitis may be prodromal findings of MEITL.

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Colorectal diffuse large B-cell lymphoma: molecular subclassification and prognostic significance of immunoglobulin gene translocation

Cited by 13 publications

References 34 publications

Genomic Mutation Profile of Primary Gastrointestinal Diffuse Large B-Cell Lymphoma

Genomic Mutation Profile of Primary Gastrointestinal Diffuse Large B-Cell Lymphoma

The Incidence and Treatment Response of Double Expression of MYC and BCL2 in Patients with Diffuse Large B-Cell Lymphoma: A Systematic Review and Meta-Analysis

Endoscopic and clinicopathological characteristics of colorectal T/NK cell lymphoma

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