PMC:4996401 / 15122-19182 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":"3.2. Follicular Lymphoma\nFollicular lymphoma (FL) is the second most common NHL subtype worldwide and possibly the most common in USA. Despite the clear differences in tumor biology, morphology, and aggressiveness when compared to DLBCL [50,51], there are some common molecular pathogenetic mechanisms among the two tumors, and more notably, by gaining new genomic aberrancies, at least 20% of FLs convert to DLBCL during time [40,52,53]. The most frequent genetic aberrancy in FL is a t(14;18)(q32;q21) translocation, which is observed in about 90% of cases and causes an over-expression of BCL2, an important antiapoptotic molecule [54]. However, BCL2 translocation is not sufficient for FL development. Furthermore, a small minority of cases lack this translocation possibly representing a genetically different subset; in fact, by SNPs array analysis it was documented that BCL2-negative FL is characterized by a more simple genomic profile than the classical BCL2-positive ones [55].\nIn 2010, by using a multiplatform approach, including conventional cytogenetic techniques, BAC array comparative genomic hybridization, and Affymetrix 500K SNP arrays, Cheung et al. [56] studied a series of 50 FL cases for which normal matched DNA was available. This approach allowed to identify, in addition to the t(14;18), eight unique balanced translocations, including t(1;11;3), t(3;16)(q27;p13), t(2;4)(p16;q28) and t(2;4). The previously reported FL-associated copy number regions identified in their study were revealed including losses of 1p32-36, 6q, and 10q, and gains of 1q, 6p, 7, 12, 18, and X. The most frequent regions affected by CN-LOH turned out to be 1p36.33 (28% of cases), 6p21.3 (20%), 12q21.2–q24.33 (16%), and 16p13.3 (24%). Such regions were similarly affected in cases with more or less complex karyotype [56,57]. Of interest, the high resolution of the SNPs array allowed to identify 45 aberrant regions affecting one gene each, including CDKN2A, CDKN2B, FHIT, KIT, PEX14, and PTPRD (Table 2) [56].\nmicroarrays-04-00551-t002_Table 2 Table 2 The most important recurrent genetic aberrations in Follicular Lymphoma (FL). * These aberrations occur in transformed follicular lymphoma (tFL). Several other studies have pointed at the recurrence of CN-LOH in FL, and the regions influenced include 1p36, 6p, 6q, 10q, 12q and 16p [58,60,61,62], which in case of acquired UPD on 1p36 and 16p were correlated with shorter overall survival and poorer progression-free survival for the former and latter, respectively [61]. In another study, the recurrent CNVs in FL were reported to be overall associated with Wnt/b-catenin signaling and G1/S checkpoint regulation [63]. Furthermore, FL showed LOH of PTPRJ gene associated with LOH of 11p11.2 as it was observed in DLBCL [46]. In this regard, importantly, SNPs array karyotyping was recently used to dissect the genetic imbalances associated with FL transformation to DLBCL [59]. With this aim, Bouska et al. [59] studied 277 lymphoma samples (198 FL and 79 transformed FL/tFL) by both SNPs and gene expression microarrays. Common recurrent chromosomal abnormalities in FL included gains of 2, 5, 7, 6p, 8, 12, 17q, 18, 21, and X and losses on 6q and 17p. Many frequent small abnormalities, including losses of 1p36.33–p36.31, 6q23.3–q24.1, and 10q23.1–q25.1 and gains of 2p16.1–p15, 8q24.13–q24.3, and 12q12–q13.13 were also observed. Noteworthy, several candidate genes that may be affected were identified, including TNFRSF14, PRDM16, and the p53-family member TP73 (Table 2). Recurrent abnormalities more frequent in tFL samples included gains of 3q27.3–q28 and chromosome 11 and losses of 9p21.3 and 15q. Overall, abnormalities associated with disease transformation appeared to impair immune surveillance, activate the NFκB pathway, and deregulate p53 and B-cell transcription factors. A total of four abnormalities, namely gain of X or Xp and losses of 6q23.2–24.1 or 6q13–15, were found to be of clinical importance, i.e., were significantly associated with an overall poor survival [59].","divisions":[{"label":"Title","span":{"begin":0,"end":24}},{"label":"Table caption","span":{"begin":2018,"end":2210}}],"tracks":[{"project":"2_test","denotations":[{"id":"27600240-11114137-69474381","span":{"begin":238,"end":240},"obj":"11114137"},{"id":"27600240-18097447-69474382","span":{"begin":241,"end":243},"obj":"18097447"},{"id":"27600240-21305641-69474383","span":{"begin":428,"end":430},"obj":"21305641"},{"id":"27600240-12406872-69474384","span":{"begin":431,"end":433},"obj":"12406872"},{"id":"27600240-18492688-69474385","span":{"begin":434,"end":436},"obj":"18492688"},{"id":"27600240-8049424-69474386","span":{"begin":635,"end":637},"obj":"8049424"},{"id":"27600240-19471018-69474387","span":{"begin":984,"end":986},"obj":"19471018"},{"id":"27600240-20544841-69474388","span":{"begin":1172,"end":1174},"obj":"20544841"},{"id":"27600240-20544841-69474389","span":{"begin":1824,"end":1826},"obj":"20544841"},{"id":"27600240-22104078-69474390","span":{"begin":1827,"end":1829},"obj":"22104078"},{"id":"27600240-20544841-69474391","span":{"begin":2013,"end":2015},"obj":"20544841"},{"id":"27600240-18703704-69474454","span":{"begin":2348,"end":2350},"obj":"18703704"},{"id":"27600240-17699855-69474455","span":{"begin":2351,"end":2353},"obj":"17699855"},{"id":"27600240-19141865-69474456","span":{"begin":2354,"end":2356},"obj":"19141865"},{"id":"27600240-17495976-69474457","span":{"begin":2357,"end":2359},"obj":"17495976"},{"id":"27600240-19141865-69474458","span":{"begin":2532,"end":2534},"obj":"19141865"},{"id":"27600240-20149759-69474459","span":{"begin":2680,"end":2682},"obj":"20149759"},{"id":"27600240-23341091-69474460","span":{"begin":2786,"end":2788},"obj":"23341091"},{"id":"27600240-24037725-69474461","span":{"begin":2939,"end":2941},"obj":"24037725"},{"id":"27600240-24037725-69474462","span":{"begin":2974,"end":2976},"obj":"24037725"},{"id":"27600240-24037725-69474463","span":{"begin":4056,"end":4058},"obj":"24037725"}],"attributes":[{"subj":"27600240-11114137-69474381","pred":"source","obj":"2_test"},{"subj":"27600240-18097447-69474382","pred":"source","obj":"2_test"},{"subj":"27600240-21305641-69474383","pred":"source","obj":"2_test"},{"subj":"27600240-12406872-69474384","pred":"source","obj":"2_test"},{"subj":"27600240-18492688-69474385","pred":"source","obj":"2_test"},{"subj":"27600240-8049424-69474386","pred":"source","obj":"2_test"},{"subj":"27600240-19471018-69474387","pred":"source","obj":"2_test"},{"subj":"27600240-20544841-69474388","pred":"source","obj":"2_test"},{"subj":"27600240-20544841-69474389","pred":"source","obj":"2_test"},{"subj":"27600240-22104078-69474390","pred":"source","obj":"2_test"},{"subj":"27600240-20544841-69474391","pred":"source","obj":"2_test"},{"subj":"27600240-18703704-69474454","pred":"source","obj":"2_test"},{"subj":"27600240-17699855-69474455","pred":"source","obj":"2_test"},{"subj":"27600240-19141865-69474456","pred":"source","obj":"2_test"},{"subj":"27600240-17495976-69474457","pred":"source","obj":"2_test"},{"subj":"27600240-19141865-69474458","pred":"source","obj":"2_test"},{"subj":"27600240-20149759-69474459","pred":"source","obj":"2_test"},{"subj":"27600240-23341091-69474460","pred":"source","obj":"2_test"},{"subj":"27600240-24037725-69474461","pred":"source","obj":"2_test"},{"subj":"27600240-24037725-69474462","pred":"source","obj":"2_test"},{"subj":"27600240-24037725-69474463","pred":"source","obj":"2_test"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"2_test","color":"#c9ec93","default":true}]}]}}