Integrated Genomic Analysis of Sézary Syndrome

Mao, Xin; Chaplin, Tracy; Young, Bryan D.

doi:10.4061/2011/980150

Cited by 6 publications

(8 citation statements)

References 56 publications

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“…Specifically, point mutations, focal deletions, and translocations of NFIA have been found in myeloproliferative neoplasms [114,115] and acute erythroid leukemia [116] (Table 3). Loss of NFIB due to 9p LOH was also reported in approximately 30% of myeloproliferative neoplasms [117][118][119], and in T-cell lymphomas (Sézary syndrome) [120]. These findings suggest a possible role for NFI in hematopoietic tumour development, as corroborated for T-cell lymphomas in an insertional mutagenesis mouse model where insertions within Nfia, Nfib and Nfic occur [121] (Table 2a).…”

Section: Hematopoietic Tumourssupporting

confidence: 56%

The convergent roles of the nuclear factor I transcription factors in development and cancer

et al. 2017

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The nuclear factor I (NFI) transcription factors play important roles during normal development and have been associated with developmental abnormalities in humans. All four family members, NFIA, NFIB, NFIC and NFIX, have a homologous DNA binding domain and function by regulating cell proliferation and differentiation via the transcriptional control of their target genes. More recently, NFI genes have also been implicated in cancer based on genomic analyses and studies of animal models in a variety of tumours across multiple organ systems. However, the association between their functions in development and in cancer is not well described. In this review, we summarise the evidence suggesting a converging role for the NFI genes in development and cancer. Our review includes all cancer types in which the NFI genes are implicated, focusing predominantly on studies demonstrating their oncogenic or tumour-suppressive potential. We conclude by presenting the challenges impeding our understanding of NFI function in cancer biology, and demonstrate how a developmental perspective may contribute towards overcoming such hurdles.

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Section: Hematopoietic Tumourssupporting

confidence: 56%

The convergent roles of the nuclear factor I transcription factors in development and cancer

et al. 2017

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“…11,[37][38][39] Indeed, data from our group 22,27 and from others [23][24][25][26]28,29,[40][41][42][43] showed the presence of more complex chromosome aberrations in aggressive CTCL than in C-ALCL. 28,44 When telomeres become critically short, it is believed that their protective function is compromised and that cells follow the flow diagram process (Figure 7) with replicative senescence, crisis, escape from crisis, and maintenance of TL.…”

Section: Discussionmentioning

confidence: 59%

“…To answer this question, genomic abnormalities were investigated in SS patient cells and cell lines, taking into consideration chromosome aberrations previously reported in SS patients by our group 27 and others. [23][24][25][26]28,29 For cases 2 and 17, AU (data not shown), c-MYC and centromere 8 fluorescent probes were chosen to investigate SS nuclei chromosomal status in combination with antibodies to delineate SS cells ( Figure 2E-H) or with peptide nucleic acid telomeric probes to evaluate TL ( Figure 2I-J). Image analysis revealed that abnormal chromosome content was restricted to both neoplastic SS T cells ( Figure 2E-H) and to nuclei with short telomeres, whereas cells with normal chromosome content showed long telomeres ( Figure 2I-J).…”

Section: Short Tl: a Hallmark Of Neoplastic Ss Cellsmentioning

confidence: 99%

“…21 In these lymphoproliferations, the neoplastic T cells involve the skin as a primary site, but with disease progression, abnormal cells may also infiltrate blood, lymph nodes, lungs, heart, liver, and spleen, except for SS, which arises suddenly as an aggressive leukemic variant. 21 Whereas recent cytogenetic studies on T-MF, SS, and C-ALCL reported the presence of genetic aberrations, [22][23][24][25][26][27][28][29] the key molecular targets underlying CTCL pathogenesis remain elusive. This lack of insight into the biology of CTCL has hindered the development of true targeted therapies.…”

Section: Introductionmentioning

confidence: 99%

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Telomerase functions beyond telomere maintenance in primary cutaneous T-cell lymphoma

Chevret¹,

Andrique²,

Prochazkova-Carlotti³

et al. 2014

Blood

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Key Points• Besides maintaining short telomeres, telomerase is required for cell proliferation and tumor growth in CTCL.Telomere erosion may be counteracted by telomerase. Here we explored telomere length (TL) and telomerase activity (TA) in primary cutaneous T-cell lymphoma (CTCL) by using quantitative polymerase chain reaction and interphase quantitative fluorescence in situ hybridization assays. Samples from patients with Sézary syndrome (SS), transformed mycosis fungoides (T-MF), and cutaneous anaplastic large cell lymphoma were studied in parallel with corresponding cell lines to evaluate the relevance of TL and TA as target candidates for diagnostic and therapeutic purposes. Compared with controls, short telomeres were observed in aggressive CTCL subtypes such as SS and T-MF and were restricted to neoplastic cells in SS. While no genomic alteration of the hTERT (human telomerase catalytic subunit) locus was observed in patients' tumor cells, TA was detected. To understand the role of telomerase in CTCL, we manipulated its expression in CTCL cell lines. Telomerase inhibition rapidly impeded in vitro cell proliferation and led to cell death, while telomerase overexpression stimulated in vitro proliferation and clonogenicity properties and favored tumor development in immunodeficient mice. Our data indicate that, besides maintenance of TL, telomerase exerts additional functions in CTCL. Therefore, targeting these functions might represent an attractive therapeutic

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“…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%).…”

Section: Mature T/nk-cell Lymphoproliferative Disordersmentioning

confidence: 99%

SNP Array in Hematopoietic Neoplasms: A Review

Song

Shao

2015

Microarrays

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Cytogenetic analysis is essential for the diagnosis and prognosis of hematopoietic neoplasms in current clinical practice. Many hematopoietic malignancies are characterized by structural chromosomal abnormalities such as specific translocations, inversions, deletions and/or numerical abnormalities that can be identified by karyotype analysis or fluorescence in situ hybridization (FISH) studies. Single nucleotide polymorphism (SNP) arrays offer high-resolution identification of copy number variants (CNVs) and acquired copy-neutral loss of heterozygosity (LOH)/uniparental disomy (UPD) that are usually not identifiable by conventional cytogenetic analysis and FISH studies. As a result, SNP arrays have been increasingly applied to hematopoietic neoplasms to search for clinically-significant genetic abnormalities. A large numbers of CNVs and UPDs have been identified in a variety of hematopoietic neoplasms. CNVs detected by SNP array in some hematopoietic neoplasms are of prognostic significance. A few specific genes in the affected regions have been implicated in the pathogenesis and may be the targets for specific therapeutic agents in the future. In this review, we summarize the current findings of application of SNP arrays in a variety of hematopoietic malignancies with an emphasis on the clinically significant genetic variants.

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Integrated Genomic Analysis of Sézary Syndrome

Cited by 6 publications

References 56 publications

The convergent roles of the nuclear factor I transcription factors in development and cancer

The convergent roles of the nuclear factor I transcription factors in development and cancer

Telomerase functions beyond telomere maintenance in primary cutaneous T-cell lymphoma

SNP Array in Hematopoietic Neoplasms: A Review

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