Clonal chromosomal abnormalities as direct evidence for clonality in nasal T/natural killer cell lymphomas

Tien, Hwei‐Fang; Su, Ih‐Jen; Tang, Jih‐Luh; Liu, Ming‐Chi; Lee, Fen‐Yu; Chen, Yao‐Chang; Chuang, Sou‐Ming

doi:10.1046/j.1365-2141.1997.752711.x

Cited by 71 publications

(47 citation statements)

References 17 publications

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“…26 Using probes specific for the centromeric region and the long arm of the chromosome 6, we found that one case showed a pattern highly suggestive for the presence of an isochromosome 6p. This aberration is very common in human retinoblastoma, 27 but has also been reported in approximately 1% of acute lymphoblastic leukemia 28 and Hodgkin's lymphoma 29 and in 6% of primary mediastinal 30 and gastric NHLs, 25 as well as in individual cases of follicular, 10 nodal diffuse large B-cell 31 and nasal T/NK NHLs 32 and of Waldenstrom's macroglobulinemia. 33 It has been suggested that, similarly to cyclin D1 in mantle cell lymphoma and plasma cell myeloma, cyclin D3 may be deregulated in hematopoietic disorders as a consequence of the t(6;14) translocation.…”

Section: Discussionmentioning

confidence: 93%

Cyclin D3 immunoreactivity in follicular lymphoma is independent of the t(6;14)(p21.1;q32.3) translocation or cyclin D3 gene amplification and is correlated with histologic grade and Ki‐67 labeling index

Pruneri

Valentini

Fabris

et al. 2004

Intl Journal of Cancer

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An abnormal expression of cyclin D3, a key regulator of the cell cycle, has been documented in a variety of human malignancies, and the cyclin D3 gene, mapping to 6p21, may be deregulated in plasma cell myeloma and non-Hodgkin's lymphoma as a result of the t(6;14)(p21.1;q32.3) translocation and/or gene amplification. In the current study, we for the first time investigated by immunohistochemistry and fluorescence in situ hybridization (FISH) the prevalence of cyclin D3 abnormalities in follicular lymphomas (FLs), comparing the results with traditional clinicopathologic characteristics, p27 and skp2 immunoreactivity (IR) and Ki-67 labeling index (LI). Cyclin D3, skp2 and Ki-67 IR significantly increased from grade I to grade III FL (p ‫؍‬ 0.0003, p ‫؍‬ 0.0001 and p < 0.0001, respectively), while p27 IR was significantly (p < 0.0001) more prevalent in low-grade tumors. Cyclin D3 IR was directly correlated with the Ki-67 LI (p < 0.0001) and inversely correlated with p27 IR (p ‫؍‬ 0.050). None of the 13 cases analyzed by FISH showed the t(6;14) translocation, but in 2 (15.3%) grade I FLs 3 cyclin D3 signals were detected. Cohybridization with probes specific for the centromeric region and the long arm of the chromosome 6 indicated trisomy in one case and a pattern highly suggestive for the presence of an isochromosome 6p in the other case. Our data suggest that the t(6;14) translocation may be extremely uncommon in FL and that a deregulated expression of cyclin D3, possibly due to epigenetic mechanisms, may be involved in the pathogenesis of high-grade tumors.

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Section: Discussionmentioning

confidence: 93%

Cyclin D3 immunoreactivity in follicular lymphoma is independent of the t(6;14)(p21.1;q32.3) translocation or cyclin D3 gene amplification and is correlated with histologic grade and Ki‐67 labeling index

Pruneri

Valentini

Fabris

et al. 2004

Intl Journal of Cancer

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“…Furthermore, there is ample evidence which implicates the role of genes around the flanking region of the break/fusion points in distinct phenotypes of many hematological disorders [4,[26][27][28][29]41]. For examples, 5p13 deletion is one of the most common regions emerging in acute lymphoblastic leukemia, lymphoblastic lymphoma, acute monoblastic leukemia, acute myleoblastic leukemia with maturation, acute myeloid leukemia, adult T-cell lymphoma/ leukemia, chronic lymphocytic leukemia, etc [4,24,25,[41][42][43][44][45]. Despite a strong implication for genes located in 5p, the molecular mechanisms underlying their deregulation in these characteristic disorders still remain unknown.…”

Section: Discussionmentioning

confidence: 99%

Genomic analysis of CD8+ NK/T cell line, ‘SRIK-NKL’, with array-based CGH (aCGH), SKY/FISH and molecular mapping

et al. 2008

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We performed aCGH, SKY /FISH, molecular mapping and expression analyses on a permanent CD8+ NK/T cell line, 'SRIK-NKL' established from a lymphoma (ALL) patient, in attempt to define the fundamental genetic profile of its unique NK phenotypes. aCGH revealed hemizygous deletion of 6p containing genes responsible for hematopoietic functions. The SKY demonstrated that a constitutive reciprocal translocation, rcpt(5;14)(p13.2;q11) is a stable marker. Using somatic hybrids containing der(5) derived from SRIK-NKL, we found that the breakpoint in one homologue of no. 5 is located upstream of IL7R and also that the breakpoint in no. 14 is located within TRA@. The FISH analysis using BAC which contains TRA@ and its flanking region further revealed a ~231 kb deletion within 14q11 in the der(5) but not in the normal homologue of no. 14. The RT-PCR analysis detected mRNA for TRA@ transcripts which were extending across, but not including, the deleted region. IL7R was detected at least at mRNA levels. These findings were consistent with the immunological findings that TRA@ and IL7R are both expressed at mRNA levels and TRA@ at cytoplasmic protein levels in SRIK-NKL cells. In addition to rept(5;14), aCGH identified novel copy number abnormalities suggesting that the unique phenotype of the SRIK-NKL cell line is not solely due to the TRA@ rearrangement. These findings provide supportive evidence for the notion that SRIK-NKL cells may be useful for studying not only the function of NK cells but also genetic deregulations associated with leukemiogenesis.

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“…Deletions of the long arm of chromosome 6 (6q) are one of the most common chromosomal abnormalities observed in various human solid (Orphanos et al, 1995;Noviello et al, 1996;Theile et al, 1996;Makino et al, 2001;Piao et al, 2001) and lymphoid malignancies (Gerard et al, 1997;Sherratt et al, 1997;Tien et al, 1997;Wong et al, 1997;Hauptschein et al, 1998;Merup et al, 1998;Amiel et al, 1999;Stilgenbauer et al, 1999;Sinclair et al, 2000;Mancini et al, 2002). Many subchromosomal regions from 6q13 to q27 have been suggested to harbour putative tumour suppressor genes for different types of tumours, examples being 6q14-21 in prostate cancer (Cooney et al, 1996), 6q16-q21 in lymphoid leukaemia (Jackson et al, 1998(Jackson et al, , 2000, 6q23.3-q25 in breast cancer, and 6q27 in B-cell non-Hodgkin lymphoma (NHL) (Hauptschein et al, 1998) and ovarian cancers (Saito et al, 1996).…”

Section: Discussionmentioning

confidence: 99%

“…Earlier studies using various techniques have reported chromosomal abnormalities in NK/T-cell lymphoma/leukaemia patients; these include gains on chromosomes Xp,8 and 20p, and deletions on 6q, 11q, 13q and 17q (Tien et al, 1997;Wong et al, 1997;Siu et al, 1999;Wong et al, 1999a;Zhang et al, 1999;Ko et al, 2001). Of these, deletion at 6q21-q25 is the most common chromosomal abnormality (Wong et al, 1997;Zhang et al, 1999), occurring in more than 90% of patients with nasal NK/T-cell lymphoma (Siu et al, 2000).…”

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confidence: 99%

A 2·6 Mb interval on chromosome 6q25.2–q25.3 is commonly deleted in human nasal natural killer/T‐cell lymphoma

Sun

Lin

et al. 2003

Br J Haematol

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Summary. Natural killer (NK)/T-cell lymphoma is a special subtype of rare malignant lymphoma that is more prevalent in Asia than in America and Europe. This newly characterized haemato-lymphoid malignancy is highly aggressive and frequently present in nasal and upper aerodigestive sites. Several studies have reported the commonly deleted region of chromosome 6q21-25 in this particular type of lymphoma. To refine the smallest region of overlapping (SRO) deletion for localization of potential tumour suppressor (TS) genes, we performed loss of heterozygosity (LOH) and homozygosity mapping of deletion (HOMOD) analyses on 37 nasal and nasal-type NK/T-cell lymphoma patients using a panel of 25 microsatellite markers, covering the 6q21-q25 region. In all patients studied, LOH was detected in eight (89%) paired-sample patients, while hemizygous deletion was detected in three (11%) singlesample patients. Combination of the LOH and HOMOD results defined a distinct 3 Mb SRO on chromosome 6q25. Quantitative multiplex polymerase chain reaction analysis of 10 sequence-tagged sites further refined the putative TS-gene-containing region to a 2AE6 Mb interval between TIAM2 and SNX9. Eighteen known genes/Unigene clusters and 25 hypothetical genes are located within this 2AE6 Mb region, but none are previously identified TS genes. These results provide a framework for future positional cloning of novel TS gene(s) at 6q25.2-q25.3.

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Clonal chromosomal abnormalities as direct evidence for clonality in nasal T/natural killer cell lymphomas

Cited by 71 publications

References 17 publications

Cyclin D3 immunoreactivity in follicular lymphoma is independent of the t(6;14)(p21.1;q32.3) translocation or cyclin D3 gene amplification and is correlated with histologic grade and Ki‐67 labeling index

Cyclin D3 immunoreactivity in follicular lymphoma is independent of the t(6;14)(p21.1;q32.3) translocation or cyclin D3 gene amplification and is correlated with histologic grade and Ki‐67 labeling index

Genomic analysis of CD8+ NK/T cell line, ‘SRIK-NKL’, with array-based CGH (aCGH), SKY/FISH and molecular mapping

A 2·6 Mb interval on chromosome 6q25.2–q25.3 is commonly deleted in human nasal natural killer/T‐cell lymphoma

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