PMC:5003446 / 50762-56279 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/5003446","sourcedb":"PMC","sourceid":"5003446","source_url":"https://www.ncbi.nlm.nih.gov/pmc/5003446","text":"10. Mature T/NK-Cell Lymphoproliferative Disorders\nThe T/NK-cell lymphoproliferative disorders comprise a diverse group of mature lymphomas or leukemias with variable etiology and clinical course. SNP array studies in this group of neoplasms are limited to a few selected types, largely due to the much lower frequency of occurrence of mature T/NK-cell leukemia/lymphoma overall. Peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS) is the most common T-cell lymphoma and morphologically, phenotypically and cytogenetically heterogeneous. Hartmann et al studied 47 cases of PTCL, NOS with a 250K SNP array, and found genomic alterations in 47% of cases, including recurrent gains of chromosome regions 1q32–43, 2p15–16, 7, 8q24, 11q14–25, 17q11–21 and 21q11–21 and losses of chromosome regions 1p35–36, 5q33, 6p22, 6q16, 6q21–22, 8p21–23, 9p21, 10p11–12, 10q11–22, 10q25–26, 13q14, 15q24, 16q22, 16q24, 17p11, 17p13, and Xp22 [120]. Genomic gains of REL gene locus at 2p15–16 and nuclear expression of the REL protein by immunohistochemistry were identified in approximately 25% cases of PTCL, NOS, suggesting pathogenetic relevance of REL in a subset of PTCL, NOS cases.\nAngioimmunoblastic T-cell lymphoma (AILT) is the second most common mature T-cell lymphoma and characterized by proliferation of malignant follicular T-helper cells associated with Epstein-Barr virus infection. In a study comparing the genomic profiles of 40 cases of AILT and 33 cases of PTCL, NOS by 50 K SNP array, three quarters of the cases had relatively stable genomes, while the remaining one quarter had CNAs of various sizes [121]. The presence of CNAs was associated with poor prognosis. Highly-recurrent chromosomal gains in both AILT and PTCL, NOS were clustered at three distinct regions of 8q, 9p, and 19q, and genomic losses at two distinct regions of 3q and 9p. The most common region of LOH was identified in a 440-kb region at 2q32.3. AILT- or PTCL NOS-specific CNAs or LOH were present at 21 regions. Furthermore, overexpression of CARMA1 at 7p22 and MYCBP2 at frequently amplified 13q22 predicted poor prognosis. A novel isoform of IKZF2 was identified in the LOH region at 2q34, which likely acted as a dominant negative form to participate in the transformation to AILT or PTCL, NOS.\nAdult T-cell leukemia/lymphoma is a well-defined malignant T-cell neoplasm caused by human T-cell leukemia virus type 1 (HTLV-1). To understand the genetic events occurring after HTLV-1 infection, spectral karyotyping and SNP array of 61 ATLL cases revealed a 2-Mb deletion region breakpoint in 10p11.2 in 35% cases [122]. Transcription Factor 8 (TCF8) was identified within this region by gene expression studies as a possible tumor suppressor for ATLL. Loss of TCF8 resulted in resistance to transforming growth factor β1 (TGF-β1) mediated growth inhibition in ATLL cells, which likely contributed to the pathogenesis of ATLL. The same group in a subsequent study showed localization of the breakpoints at 10p11.2 within the EPC1 locus by SNP array in two cases [123]. EPC1 is a member of the polycomb group gene family and participate in chromatin formation and gene regulation. EPC1/ASXL2 and truncated EPC1 were identified in the two cases respectively, and both were able to induce cellular proliferation in in vitro studies, implicating EPC1 in the pathogenesis of ATLL in some cases.\nT-cell prolymphocytic leukemia (T-PLL) is an aggressive T-cell leukemia characterized by proliferation of prolymphocytes in the peripheral blood, bone marrow, liver, spleen and lymph nodes. The most frequent genetic change is inversion of chromosome 14. Gains in 6p (3/12), 8q (10/12), and of losses in 6q (5/12), 8p (7/12), 10p (4/12), 11q (3/12), and 18p (3/12) were identified by a 50K SNP array when analyzing 11 T-PLL with inv(14)(q11q32) or t(14;14)(q11;q32) and one T-PLL case without inv(14)/t(14;14) [124]. Recurrent UPD in 3q, and non-recurrent partial UPD on chromosomes 3, 6, 9, 11, and 13 were identified. In a subsequent study of 18 cases of T-PLL by 250K SNP array, Nowak et al. [125] identified abundant copy number alterations, and confirmed the characteristic genetic lesions described before. Recurrent microdeletions targeting microRNA 34b/c, ETS1, and FLI1 were implicated in losses in chromosome 11, and PLEKHA2, NBS1, NOV and MYST3 genes were found to be involved in the breakpoints of chromosome 8. New recurrent lesions were identified on chromosomes 5p, 12p, 13q, 17, and 22 including aUPD on chromosome 17q, with genes DNAH5, ETV6, miR-15a, and miR-16-1, p53, BIRC5, and SOCS3 implicated in the regions. Future studies of the implicated genes identified by SNP array are likely going to further our understanding of the pathogenesis and provide potential targets for therapy.\nSézary syndrome (SS) is rare but aggressive neoplasm characterized by erythroderma, generalized adenopathy, and infiltrate of cerebriform Sézary cells in the peripheral blood, skin and lymph nodes. A low resolution 10K SNP array of eight patients with SS identified frequent SNP copy number changes and LOH involving 1, 2p, 3, 4q, 5q, 6, 7p, 8, 9, 10, 11, 12q, 13, 14, 16q, 17, and 20 [126]. SNP copy number loss was most frequent at FAT gene at 4q35 (75%), followed by VEGFC at 4q34.1q34.3 (50%), NFIB at chromosome 12 (38%), and TRIM16 at 17p11.2 (38%). SNP LOH gene clusters at chromosome regions of 9q31q34, 10p11q26, and 13q11q12 were only present in SS but not in normal controls, suggesting their involvement in SS pathology.","divisions":[{"label":"Title","span":{"begin":0,"end":50}}],"tracks":[{"project":"2_test","denotations":[{"id":"27600067-19863542-69477938","span":{"begin":938,"end":941},"obj":"19863542"},{"id":"27600067-18633432-69477939","span":{"begin":1619,"end":1622},"obj":"18633432"},{"id":"27600067-18467597-69477940","span":{"begin":2607,"end":2610},"obj":"18467597"},{"id":"27600067-19484761-69477941","span":{"begin":3055,"end":3058},"obj":"19484761"},{"id":"27600067-17713554-69477942","span":{"begin":3892,"end":3895},"obj":"17713554"},{"id":"27600067-19278963-69477943","span":{"begin":4077,"end":4080},"obj":"19278963"},{"id":"27600067-22567373-69477944","span":{"begin":5171,"end":5174},"obj":"22567373"}],"attributes":[{"subj":"27600067-19863542-69477938","pred":"source","obj":"2_test"},{"subj":"27600067-18633432-69477939","pred":"source","obj":"2_test"},{"subj":"27600067-18467597-69477940","pred":"source","obj":"2_test"},{"subj":"27600067-19484761-69477941","pred":"source","obj":"2_test"},{"subj":"27600067-17713554-69477942","pred":"source","obj":"2_test"},{"subj":"27600067-19278963-69477943","pred":"source","obj":"2_test"},{"subj":"27600067-22567373-69477944","pred":"source","obj":"2_test"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"2_test","color":"#ec93a1","default":true}]}]}}