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Integrative genomic and transcriptomic analysis identified candidate genes implicated in the pathogenesis of hepatosplenic T-cell lymphoma

(2014) PLOS ONE. 9(7).
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Abstract
Hepatosplenic T-cell lymphoma (HSTL) is an aggressive lymphoma cytogenetically characterized by isochromosome 7q [i(7)(q10)], of which the molecular consequences remain unknown. We report here results of an integrative genomic and transcriptomic (expression microarray and RNA-sequencing) study of six i(7)(q10)-positive HSTL cases, including HSTL-derived cell line (DERL-2), and three cases with ring 7 [r(7)], the recently identified rare variant aberration. Using high resolution array CGH, we profiled all cases and mapped the common deleted region (CDR) at 7p22.1p14.1 (34.88 Mb; 3506316-38406226 bp) and the common gained region (CGR) at 7q22.11q31.1 (38.77 Mb; 86259620-124892276 bp). Interestingly, CDR spans a smaller region of 13 Mb (86259620-99271246 bp) constantly amplified in cases with r(7). In addition, we found that TCRG (7p14.1) and TCRB (7q32) are involved in formation of r(7), which seems to be a byproduct of illegitimate somatic rearrangement of both loci. Further transcriptomic analysis has not identified any CDR-related candidate tumor suppressor gene. Instead, loss of Delta 7p22.1p14.1 correlated with an enhanced expression of CHN2 (7p14.1) and the encoded beta 2-chimerin. Gain and amplification of 7q22.11q31.1 are associated with an increased expression of several genes postulated to be implicated in cancer, including RUNDC3B, PPP1R9A and ABCB1, a known multidrug resistance gene. RNA-sequencing did not identify any disease-defining mutation or gene fusion. Thus, chromosome 7 imbalances remain the only driver events detected in this tumor. We hypothesize that the Delta 7p22.1p14.1-associated enhanced expression of CHN2/beta 2-chimerin leads to downmodulation of the NFAT pathway and a proliferative response, while upregulation of the CGR-related genes provides growth advantage for neoplastic delta gamma T-cells and underlies their intrinsic chemoresistance. Finally, our study confirms the previously described gene expression profile of HSTL and identifies a set of 24 genes, including three located on chromosome 7 (CHN2, ABCB1 and PPP1R9A), distinguishing HSTL from other malignancies.
Keywords
TUMOR-SUPPRESSOR GENES, ATP-DEFICIENT MICE, GAMMA/DELTA-LYMPHOMA, ISOCHROMOSOME 7Q, HEPATOCELLULAR-CARCINOMA, NUCLEAR FACTOR, MOLECULAR CHARACTERIZATION, CHROMOSOMAL-ABERRATION, IMMUNOLOGICAL SYNAPSE, MULTIDRUG-RESISTANCE

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MLA
Ferreiro, Julio Finalet et al. “Integrative Genomic and Transcriptomic Analysis Identified Candidate Genes Implicated in the Pathogenesis of Hepatosplenic T-cell Lymphoma.” PLOS ONE 9.7 (2014): n. pag. Print.
APA
Ferreiro, J. F., Rouhigharabaei, L., Urbankova, H., van der Krogt, J.-A., Michaux, L., Shetty, S., Krenacs, L., et al. (2014). Integrative genomic and transcriptomic analysis identified candidate genes implicated in the pathogenesis of hepatosplenic T-cell lymphoma. PLOS ONE, 9(7).
Chicago author-date
Ferreiro, Julio Finalet, Leila Rouhigharabaei, Helena Urbankova, Jo-Anne van der Krogt, Lucienne Michaux, Shashirekha Shetty, Laszlo Krenacs, et al. 2014. “Integrative Genomic and Transcriptomic Analysis Identified Candidate Genes Implicated in the Pathogenesis of Hepatosplenic T-cell Lymphoma.” Plos One 9 (7).
Chicago author-date (all authors)
Ferreiro, Julio Finalet, Leila Rouhigharabaei, Helena Urbankova, Jo-Anne van der Krogt, Lucienne Michaux, Shashirekha Shetty, Laszlo Krenacs, Thomas Tousseyn, Pascale De Paepe, Anne Uyttebroeck, Gregor Verhoef, Tom Taghon, Peter Vandenberghe, Jan Cools, and Iwona Wlodarska. 2014. “Integrative Genomic and Transcriptomic Analysis Identified Candidate Genes Implicated in the Pathogenesis of Hepatosplenic T-cell Lymphoma.” Plos One 9 (7).
Vancouver
1.
Ferreiro JF, Rouhigharabaei L, Urbankova H, van der Krogt J-A, Michaux L, Shetty S, et al. Integrative genomic and transcriptomic analysis identified candidate genes implicated in the pathogenesis of hepatosplenic T-cell lymphoma. PLOS ONE. 2014;9(7).
IEEE
[1]
J. F. Ferreiro et al., “Integrative genomic and transcriptomic analysis identified candidate genes implicated in the pathogenesis of hepatosplenic T-cell lymphoma,” PLOS ONE, vol. 9, no. 7, 2014.
@article{5801571,
  abstract     = {Hepatosplenic T-cell lymphoma (HSTL) is an aggressive lymphoma cytogenetically characterized by isochromosome 7q [i(7)(q10)], of which the molecular consequences remain unknown. We report here results of an integrative genomic and transcriptomic (expression microarray and RNA-sequencing) study of six i(7)(q10)-positive HSTL cases, including HSTL-derived cell line (DERL-2), and three cases with ring 7 [r(7)], the recently identified rare variant aberration. Using high resolution array CGH, we profiled all cases and mapped the common deleted region (CDR) at 7p22.1p14.1 (34.88 Mb; 3506316-38406226 bp) and the common gained region (CGR) at 7q22.11q31.1 (38.77 Mb; 86259620-124892276 bp). Interestingly, CDR spans a smaller region of 13 Mb (86259620-99271246 bp) constantly amplified in cases with r(7). In addition, we found that TCRG (7p14.1) and TCRB (7q32) are involved in formation of r(7), which seems to be a byproduct of illegitimate somatic rearrangement of both loci. Further transcriptomic analysis has not identified any CDR-related candidate tumor suppressor gene. Instead, loss of Delta 7p22.1p14.1 correlated with an enhanced expression of CHN2 (7p14.1) and the encoded beta 2-chimerin. Gain and amplification of 7q22.11q31.1 are associated with an increased expression of several genes postulated to be implicated in cancer, including RUNDC3B, PPP1R9A and ABCB1, a known multidrug resistance gene. RNA-sequencing did not identify any disease-defining mutation or gene fusion. Thus, chromosome 7 imbalances remain the only driver events detected in this tumor. We hypothesize that the Delta 7p22.1p14.1-associated enhanced expression of CHN2/beta 2-chimerin leads to downmodulation of the NFAT pathway and a proliferative response, while upregulation of the CGR-related genes provides growth advantage for neoplastic delta gamma T-cells and underlies their intrinsic chemoresistance. Finally, our study confirms the previously described gene expression profile of HSTL and identifies a set of 24 genes, including three located on chromosome 7 (CHN2, ABCB1 and PPP1R9A), distinguishing HSTL from other malignancies.},
  articleno    = {e102977},
  author       = {Ferreiro, Julio Finalet and Rouhigharabaei, Leila and Urbankova, Helena and van der Krogt, Jo-Anne and Michaux, Lucienne and Shetty, Shashirekha and Krenacs, Laszlo and Tousseyn, Thomas and De Paepe, Pascale and Uyttebroeck, Anne and Verhoef, Gregor and Taghon, Tom and Vandenberghe, Peter and Cools, Jan and Wlodarska, Iwona},
  issn         = {1932-6203},
  journal      = {PLOS ONE},
  keywords     = {TUMOR-SUPPRESSOR GENES,ATP-DEFICIENT MICE,GAMMA/DELTA-LYMPHOMA,ISOCHROMOSOME 7Q,HEPATOCELLULAR-CARCINOMA,NUCLEAR FACTOR,MOLECULAR CHARACTERIZATION,CHROMOSOMAL-ABERRATION,IMMUNOLOGICAL SYNAPSE,MULTIDRUG-RESISTANCE},
  language     = {eng},
  number       = {7},
  pages        = {17},
  title        = {Integrative genomic and transcriptomic analysis identified candidate genes implicated in the pathogenesis of hepatosplenic T-cell lymphoma},
  url          = {http://dx.doi.org/10.1371/journal.pone.0102977},
  volume       = {9},
  year         = {2014},
}

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