Significance of Bcl10 gene mutations in the clinical diagnosis of MALT-type ocular adnexal lymphoma in the Chinese population

Abstract

ABSTRACT. We investigated the expression of Bcl10 gene mutations in mucosa-associated lymphoid tissue-type ocular adnexal lymphoma (OAL), atypical lymphoid hyperplasia (ALH), and reactive lymphoid hyperplasia (RLH) in the Chinese population and its role in clinical diagnosis and pathogenesis. Forty-three samples were collected during patient surgeries. Pathological diagnosis confirmed OAL in 23 cases, ALH in 10 cases, and RLH in 10 cases. Normal peripheral lymph tissues from 12 cases were used as negative controls. Bcl10 gene expression was examined using molecular biological methods, and DNA sequences and mutations were compared with published data. The protein expression of Bcl10 and nuclear factor kappaB (NF-κB) were detected with immunohistological and immunofluorescence colocalization. Bcl10 gene expression was detected in 15 OAL cases. Novel mutations were found in 11 cases. Notably, 1 mutation, which matched a published mutation, was detected in 1 ALH case; 1 novel mutation was found in 1 RLH case; and no Bcl10 gene mutation was found in controls. Most novel mutations were This report is the first of newly discovered mutations in the Bcl10 gene in the Chinese population. The distribution of the mutations is consistent with and more sensitive than that of the pathological diagnosis. These mutations can be used to identify the stage and clinical characteristics even when morphological changes are absent.

Identifying Genetic Lesions in Ocular Adnexal Extranodal Marginal Zone Lymphomas of the MALT Subtype by Whole Genome, Whole Exome and Targeted Sequencing

“…Previous studies on somatic mutations and chromosomal abnormalities in OAML mostly focused on candidate gene approaches, interrogating genetic lesions that were known from other types of B cell lymphomas [10,11,[14][15][16][25][26][27]. This led to major insights into recurrent gene mutations, chromosomal translocations, and copy number gains and losses in OAML.…”

“…As these translocations promote constitutive NF-κB activity [9,10,12], which is a hallmark of MALT lymphomas [13], several studies searched for further mutations in components of the NF-κB pathway in OAML. Indeed, recurrent mutations were found in TNFAIP3 (around 30% of cases), MYD88 (around 5-20% of cases), and BCL10 (around 25% of cases in a cohort of patients from China), whereas other genes were rarely or not mutated in the cases analyzed [14,15]. We recently showed that also NFKBIA is recurrently mutated in such lymphomas [16].…”

Kappa and lambda immunohistochemistry and in situ hybridization in the evaluation of atypical cutaneous lymphoid infiltrates

“…Sixty-three relevant articles assessing kappa and lambda IHC or ISH in the evaluation of an atypical cutaneous or mucosal lymphoid infiltrate were identified ( Table 1, Table S1). 5,[9][10][11][12][13][14][15][16][17][18] 44 papers evaluated IHC exclusively, 10,11,13,15,17,[22][23][24][25][26][27][28][29]31,32,34,35,37,40,42,45,46,[48][49][50][52][53][54][55][57][58][59][60][61][62][63][64][65][66]…”

“…Figure 1A-F). 5,9,11,13,14,[16][17][18][22][23][24][28][29][30][31][32][33]35,38,39,41,43,44,49,50,[52][53][54]58,[60][61][62][63][64]66,68,69,72,73 16 papers exclusively examined primary cutaneous marginal zone lymphoma with kappa and lambda IHC/ISH, including lesions termed immunocytomas, amyloidomas, primary cutaneous plasmacytomas, and cutaneous follicular lymphoid hyperplasia with monotypic plasma cells. 13,14,18,24,29,30,32,43,44,[52][53]…”

“…5,15,28,41,48,70,71 Eleven papers examined kappa and lambda restriction in mucosal lesions, including oral, ocular and genital mucosa. 9,10,23,28,33,35,45,50,56,58,60 When histopathologic features were fully described, plasma cells were inconspicuous to absent in FCL, 28,37,41 MCL, 28 DLBCL, 37,41 and most cases of CLL/SLL, 25,26,39,55 and light chain restriction was recognized in some cases by weak staining of Bcells. 31,41 Non-neoplastic infiltrates examined using kappa and lambda IHC and ISH included reactive lymphoid hyperplasia (cutaneous lymphoid hyperplasia, atypical lymphoid hyperplasia, "lymphocytoma F I G U R E 1 Primary cutaneous marginal zone lymphoma.…”