PMC:4996401 / 26146-29545 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/4996401","sourcedb":"PMC","sourceid":"4996401","source_url":"https://www.ncbi.nlm.nih.gov/pmc/4996401","text":"3.5. Peripheral T Cell Lymphomas\nPeripheral T cell lymphomas (PTCLs) are a heterogeneous group of cancers characterized by extremely variable morphology, phenotype, genetic and clinical features. The latter, however, mainly consist in very aggressive behavior and poor clinical outcome for most nodal tumors [77,78]. As the majority of PTCLs cannot be currently classified within a specific group based on morphology, phenotype, genetics and clinical features, they were included within the not otherwise specified group (PTCL/NOS) [79]. The latter, together with angioimmunoblastic T-cell lymphoma (AITL) and anaplastic large cell lymphomas (ALCL) ALK-positive and ALK-negative, represent the commonest nodal PTCL. Probably due to their rarity in Western countries, where they account for not more than 10% of all NHL, only relatively few genomic studies have been performed in this setting, specially based on SNPs arrays [80,81,82]. In 2008, Fujiwara et al. [80] used a GeneChip 50k SNP array to evaluate genetic perturbations in PTCL/NOS and AITL. They recognized some recurrent gains and losses, with chromosomal regions 8q24, 9p23 and 19q13 for the former and 9p21 for the latter (Table 5). Interestingly, the recurrent loss mapped to CDKN2A and CDKN2B, two important inhibitors of cyclin-dependent kinases with established role in human cancers. Subsequently, our group, by using the Affymetrix 250k GeneChip SNP array could achieve a higher resolution in defining the recurrent CNV and provided some additional details as far PTCL/NOS were concerned [81]. Indeed, we recognized a set of recurrent imbalances, including gains on chromosome 1, 2, 7, 8, 11, 17 and 21, and losses on chromosomes 1, 5, 6, 8, 9, 10, 13, 15, 16, 17 and X chromosome. Interestingly, genomic imbalances affected several regions containing members of nuclear factor-κ (NFκB) signaling. Particularly, gains of 2p15-16 were found and confirmed by FISH in three cases and were associated with breakpoints at the REL locus. Nuclear expression (i.e., activation) of the encoded REL protein was then documented by immunohistochemistry. These findings were in line with what previously observed by gene expression profiling in PTCL/NOS and with the general notion that NFκB is activated in a fraction of cases with possible prognostic impact [83,84,85,86]. Further, recurrent genomic imbalances appeared to affect and genes involved in cell cycle control such as RB1, TP53, CDK6 and CDKN2A-B (Table 5) [81].\nmicroarrays-04-00551-t005_Table 5 Table 5 The most important recurrent genetic aberrations in Peripheral T cell lymphomas (PTCLs). More recently, a high-density SNPs array was applied to a series of 64 ALCLs [82], the third most common nodal PTCL subtype. The authors found that the commonest lesions were losses at 17p13 and at 6q21, encompassing the TP53 and PRDM1 genes, respectively. The latter gene, encoding for BLIMP1, was inactivated by multiple mechanisms, more frequently, but not exclusively, in ALK-negative/ALCL. In vitro and in vivo experiments showed that that PRDM1 is a tumor suppressor gene in ALCL models, likely acting as an anti-apoptotic agent. Losses of TP53 and/or PRDM1 were present in 52% of ALK-negative/ALCL, and in 29% of all ALCL cases. Of clinical relevance, the group of patients with ALK-negative/ALCL and bearing PRDM1 and/or 17p loss presented an inferior overall survival [82].","divisions":[{"label":"Title","span":{"begin":0,"end":32}},{"label":"Table caption","span":{"begin":2483,"end":2616}}],"tracks":[{"project":"2_test","denotations":[{"id":"27600240-23023716-69474537","span":{"begin":309,"end":311},"obj":"23023716"},{"id":"27600240-24481943-69474538","span":{"begin":312,"end":314},"obj":"24481943"},{"id":"27600240-18755717-69474539","span":{"begin":533,"end":535},"obj":"18755717"},{"id":"27600240-18633432-69474540","span":{"begin":925,"end":927},"obj":"18633432"},{"id":"27600240-19863542-69474541","span":{"begin":928,"end":930},"obj":"19863542"},{"id":"27600240-24004669-69474542","span":{"begin":931,"end":933},"obj":"24004669"},{"id":"27600240-18633432-69474543","span":{"begin":962,"end":964},"obj":"18633432"},{"id":"27600240-19863542-69474544","span":{"begin":1559,"end":1561},"obj":"19863542"},{"id":"27600240-16270046-69474545","span":{"begin":2318,"end":2320},"obj":"16270046"},{"id":"27600240-17304354-69474546","span":{"begin":2321,"end":2323},"obj":"17304354"},{"id":"27600240-18006812-69474547","span":{"begin":2324,"end":2326},"obj":"18006812"},{"id":"27600240-23536439-69474548","span":{"begin":2327,"end":2329},"obj":"23536439"},{"id":"27600240-19863542-69474549","span":{"begin":2478,"end":2480},"obj":"19863542"},{"id":"27600240-24004669-69474564","span":{"begin":2695,"end":2697},"obj":"24004669"},{"id":"27600240-24004669-69474565","span":{"begin":3395,"end":3397},"obj":"24004669"}],"attributes":[{"subj":"27600240-23023716-69474537","pred":"source","obj":"2_test"},{"subj":"27600240-24481943-69474538","pred":"source","obj":"2_test"},{"subj":"27600240-18755717-69474539","pred":"source","obj":"2_test"},{"subj":"27600240-18633432-69474540","pred":"source","obj":"2_test"},{"subj":"27600240-19863542-69474541","pred":"source","obj":"2_test"},{"subj":"27600240-24004669-69474542","pred":"source","obj":"2_test"},{"subj":"27600240-18633432-69474543","pred":"source","obj":"2_test"},{"subj":"27600240-19863542-69474544","pred":"source","obj":"2_test"},{"subj":"27600240-16270046-69474545","pred":"source","obj":"2_test"},{"subj":"27600240-17304354-69474546","pred":"source","obj":"2_test"},{"subj":"27600240-18006812-69474547","pred":"source","obj":"2_test"},{"subj":"27600240-23536439-69474548","pred":"source","obj":"2_test"},{"subj":"27600240-19863542-69474549","pred":"source","obj":"2_test"},{"subj":"27600240-24004669-69474564","pred":"source","obj":"2_test"},{"subj":"27600240-24004669-69474565","pred":"source","obj":"2_test"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"2_test","color":"#ec93dc","default":true}]}]}}