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Sub-megabase resolution tiling (SMRT) array-based comparative genomic hybridization profiling reveals novel gains and losses of chromosomal regions in Hodgkin Lymphoma and Anaplastic Large Cell Lymphoma cell lines.

Fadlelmola FM, Zhou M, de Leeuw RJ, Dosanjh NS, Harmer K, Huntsman D, Lam WL, Banerjee D - Mol. Cancer (2008)

Bottom Line: Assessment of copy number alterations with 26,819 DNA segments identified an average of 20 genetic alterations.These are novel findings that have not been previously reported in the lymphoma literature, and opens up an entirely new area of research that has not been previously associated with lymphoma biology.The findings raise interesting possibilities about the role of signaling pathways triggered by membrane associated serine proteases in HL and aggressive NHL, similar to those described in epithelial tumors.

View Article: PubMed Central - HTML - PubMed

Affiliation: Centre for Translational and Applied Genomics (CTAG), Department of Pathology and Laboratory Medicine, British Columbia Cancer Agency, Vancouver Cancer Centre, Vancouver, BC, V5Z 4E6, Canada. ffadlelmola@bccancer.bc.ca

ABSTRACT

Background: Hodgkin lymphoma (HL) and Anaplastic Large Cell Lymphoma (ALCL), are forms of malignant lymphoma defined by unique morphologic, immunophenotypic, genotypic, and clinical characteristics, but both overexpress CD30. We used sub-megabase resolution tiling (SMRT) array-based comparative genomic hybridization to screen HL-derived cell lines (KMH2 and L428) and ALCL cell lines (DEL and SR-786) in order to identify disease-associated gene copy number gains and losses.

Results: Significant copy number gains and losses were observed on several chromosomes in all four cell lines. Assessment of copy number alterations with 26,819 DNA segments identified an average of 20 genetic alterations. Of the recurrent minimally altered regions identified, 11 (55%) were within previously published regions of chromosomal alterations in HL and ALCL cell lines while 9 (45%) were novel alterations not previously reported. HL cell lines L428 and KMH2 shared gains in chromosome cytobands 2q23.1-q24.2, 7q32.2-q36.3, 9p21.3-p13.3, 12q13.13-q14.1, and losses in 13q12.13-q12.3, and 18q21.32-q23. ALCL cell lines SR-786 and DEL, showed gains in cytobands 5p15.32-p14.3, 20p12.3-q13.11, and 20q13.2-q13.32. Both pairs of HL and ALCL cell lines showed losses in 18q21.32-18q23.

Conclusion: This study is considered to be the first one describing HL and ALCL cell line genomes at sub-megabase resolution. This high-resolution analysis allowed us to propose novel candidate target genes that could potentially contribute to the pathogenesis of HL and ALCL. FISH was used to confirm the amplification of all three isoforms of the trypsin gene (PRSS1/PRSS2/PRSS3) in KMH2 and L428 (HL) and DEL (ALCL) cell lines. These are novel findings that have not been previously reported in the lymphoma literature, and opens up an entirely new area of research that has not been previously associated with lymphoma biology. The findings raise interesting possibilities about the role of signaling pathways triggered by membrane associated serine proteases in HL and aggressive NHL, similar to those described in epithelial tumors.

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Genomic profiles of chromosome 9 for the cell lines KMH2, L428, DEL and SR-786. Data points to left and right of center purple line represents genetic losses and gains in the above mentioned cell lines. Green and red lines are scale bars at log2 ratios of -1.0 and 1.0 respectively.
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Figure 2: Genomic profiles of chromosome 9 for the cell lines KMH2, L428, DEL and SR-786. Data points to left and right of center purple line represents genetic losses and gains in the above mentioned cell lines. Green and red lines are scale bars at log2 ratios of -1.0 and 1.0 respectively.

Mentions: Chromosomes 7 and 9 showed amplification of isoforms of the trypsin gene in the KMH2 (7q32.2-q36.3), L428 (7q34-q35) and DEL (7q11.1-q36.3) cell lines but not in SR-786 in the case of PRSS1/PRSS2, whereas PRSS3 showed amplification in HL cell lines (KMH2 at 9p21.1-p13.3 and L428 at 9p21.1-p12) but not in ALCL cell lines as shown in Figures 2 and 3. These findings were confirmed by FISH analysis as shown in Figure 4. These are novel findings that have not been previously reported in the lymphoma literature, and opens up an entirely new area of research that has not been associated with lymphoma biology. The observations raise interesting possibilities about the role of signaling pathways triggered by membrane associated serine proteases in HL and ALCL, similar to those implicated in epithelial tumors [24]. Confirmation of these findings could lead to novel therapeutic approaches in HL and NHL.


Sub-megabase resolution tiling (SMRT) array-based comparative genomic hybridization profiling reveals novel gains and losses of chromosomal regions in Hodgkin Lymphoma and Anaplastic Large Cell Lymphoma cell lines.

Fadlelmola FM, Zhou M, de Leeuw RJ, Dosanjh NS, Harmer K, Huntsman D, Lam WL, Banerjee D - Mol. Cancer (2008)

Genomic profiles of chromosome 9 for the cell lines KMH2, L428, DEL and SR-786. Data points to left and right of center purple line represents genetic losses and gains in the above mentioned cell lines. Green and red lines are scale bars at log2 ratios of -1.0 and 1.0 respectively.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2254646&req=5

Figure 2: Genomic profiles of chromosome 9 for the cell lines KMH2, L428, DEL and SR-786. Data points to left and right of center purple line represents genetic losses and gains in the above mentioned cell lines. Green and red lines are scale bars at log2 ratios of -1.0 and 1.0 respectively.
Mentions: Chromosomes 7 and 9 showed amplification of isoforms of the trypsin gene in the KMH2 (7q32.2-q36.3), L428 (7q34-q35) and DEL (7q11.1-q36.3) cell lines but not in SR-786 in the case of PRSS1/PRSS2, whereas PRSS3 showed amplification in HL cell lines (KMH2 at 9p21.1-p13.3 and L428 at 9p21.1-p12) but not in ALCL cell lines as shown in Figures 2 and 3. These findings were confirmed by FISH analysis as shown in Figure 4. These are novel findings that have not been previously reported in the lymphoma literature, and opens up an entirely new area of research that has not been associated with lymphoma biology. The observations raise interesting possibilities about the role of signaling pathways triggered by membrane associated serine proteases in HL and ALCL, similar to those implicated in epithelial tumors [24]. Confirmation of these findings could lead to novel therapeutic approaches in HL and NHL.

Bottom Line: Assessment of copy number alterations with 26,819 DNA segments identified an average of 20 genetic alterations.These are novel findings that have not been previously reported in the lymphoma literature, and opens up an entirely new area of research that has not been previously associated with lymphoma biology.The findings raise interesting possibilities about the role of signaling pathways triggered by membrane associated serine proteases in HL and aggressive NHL, similar to those described in epithelial tumors.

View Article: PubMed Central - HTML - PubMed

Affiliation: Centre for Translational and Applied Genomics (CTAG), Department of Pathology and Laboratory Medicine, British Columbia Cancer Agency, Vancouver Cancer Centre, Vancouver, BC, V5Z 4E6, Canada. ffadlelmola@bccancer.bc.ca

ABSTRACT

Background: Hodgkin lymphoma (HL) and Anaplastic Large Cell Lymphoma (ALCL), are forms of malignant lymphoma defined by unique morphologic, immunophenotypic, genotypic, and clinical characteristics, but both overexpress CD30. We used sub-megabase resolution tiling (SMRT) array-based comparative genomic hybridization to screen HL-derived cell lines (KMH2 and L428) and ALCL cell lines (DEL and SR-786) in order to identify disease-associated gene copy number gains and losses.

Results: Significant copy number gains and losses were observed on several chromosomes in all four cell lines. Assessment of copy number alterations with 26,819 DNA segments identified an average of 20 genetic alterations. Of the recurrent minimally altered regions identified, 11 (55%) were within previously published regions of chromosomal alterations in HL and ALCL cell lines while 9 (45%) were novel alterations not previously reported. HL cell lines L428 and KMH2 shared gains in chromosome cytobands 2q23.1-q24.2, 7q32.2-q36.3, 9p21.3-p13.3, 12q13.13-q14.1, and losses in 13q12.13-q12.3, and 18q21.32-q23. ALCL cell lines SR-786 and DEL, showed gains in cytobands 5p15.32-p14.3, 20p12.3-q13.11, and 20q13.2-q13.32. Both pairs of HL and ALCL cell lines showed losses in 18q21.32-18q23.

Conclusion: This study is considered to be the first one describing HL and ALCL cell line genomes at sub-megabase resolution. This high-resolution analysis allowed us to propose novel candidate target genes that could potentially contribute to the pathogenesis of HL and ALCL. FISH was used to confirm the amplification of all three isoforms of the trypsin gene (PRSS1/PRSS2/PRSS3) in KMH2 and L428 (HL) and DEL (ALCL) cell lines. These are novel findings that have not been previously reported in the lymphoma literature, and opens up an entirely new area of research that has not been previously associated with lymphoma biology. The findings raise interesting possibilities about the role of signaling pathways triggered by membrane associated serine proteases in HL and aggressive NHL, similar to those described in epithelial tumors.

Show MeSH
Related in: MedlinePlus