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Clonal heterogeneity of lymphoid malignancies correlates with poor prognosis.

Suguro M, Yoshida N, Umino A, Kato H, Tagawa H, Nakagawa M, Fukuhara N, Karnan S, Takeuchi I, Hocking TD, Arita K, Karube K, Tsuzuki S, Nakamura S, Kinoshita T, Seto M - Cancer Sci. (2014)

Bottom Line: Clonal heterogeneity in lymphoid malignancies has been recently reported in adult T-cell lymphoma/leukemia, peripheral T-cell lymphoma, not otherwise specified, and mantle cell lymphoma.To determine the presence of clonal heterogeneity, 332 cases were examined using array comparative genomic hybridization analysis.Survival analysis revealed that mantle cell lymphoma and diffuse large B-cell lymphoma with clonal heterogeneity showed significantly poorer prognosis, and that clonal heterogeneity was confirmed as an independent predictor of poor prognosis for both types of lymphoma.

View Article: PubMed Central - PubMed

Affiliation: Division of Molecular Medicine, Aichi Cancer Center Research Institute, Nagoya, Japan.

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Results of array comparative genomic hybridization (CGH) analysis for cases with and without clonal heterogeneity. (a) A case without clonal heterogeneity showing a constant log2 ratio for all copy number alterations (CNA). (Top) The result of array CGH analysis with chromosomal regions on the x-axis and log2 ratios on the y-axis. There are four CNA (arrowheads) whose log2 ratios are −0.57. (Bottom) Log2 ratio and tumor cell population. The population of tumor cells with the CNA whose log2 ratio is −0.57 is calculated as 65% (Fig. S1a–c). This case is assessed as a sample without clonal heterogeneity since populations of tumor cells with each and every CNA in this sample are the same. (b) A case with clonal heterogeneity showing different log2 ratios. (Top) The result of array CGH analysis. There are two CNA (red up arrowheads) whose log2 ratio is 0.25, five CNA (red down arrowheads) whose log2 ratios are −0.30, and two CNA (black down arrowheads) whose log2 ratios are −0.62. (Bottom left) Log2 ratios and assessed tumor cell populations. This case is assessed as a sample with clonal heterogeneity because of the different tumor cell populations. (Bottom right) The simplest model of a tumor biopsy sample with different log2 ratios explained by clonal evolution. The solid box shows a tumor biopsy sample from a patient. It consists of 30% of normal cells (30%) and 70% of tumor cells (70%, dotted box). The tumor cells consist of a subclone (32%, left) and the other subclone (38%, right), which can have evolved from the subclone in the left.
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fig01: Results of array comparative genomic hybridization (CGH) analysis for cases with and without clonal heterogeneity. (a) A case without clonal heterogeneity showing a constant log2 ratio for all copy number alterations (CNA). (Top) The result of array CGH analysis with chromosomal regions on the x-axis and log2 ratios on the y-axis. There are four CNA (arrowheads) whose log2 ratios are −0.57. (Bottom) Log2 ratio and tumor cell population. The population of tumor cells with the CNA whose log2 ratio is −0.57 is calculated as 65% (Fig. S1a–c). This case is assessed as a sample without clonal heterogeneity since populations of tumor cells with each and every CNA in this sample are the same. (b) A case with clonal heterogeneity showing different log2 ratios. (Top) The result of array CGH analysis. There are two CNA (red up arrowheads) whose log2 ratio is 0.25, five CNA (red down arrowheads) whose log2 ratios are −0.30, and two CNA (black down arrowheads) whose log2 ratios are −0.62. (Bottom left) Log2 ratios and assessed tumor cell populations. This case is assessed as a sample with clonal heterogeneity because of the different tumor cell populations. (Bottom right) The simplest model of a tumor biopsy sample with different log2 ratios explained by clonal evolution. The solid box shows a tumor biopsy sample from a patient. It consists of 30% of normal cells (30%) and 70% of tumor cells (70%, dotted box). The tumor cells consist of a subclone (32%, left) and the other subclone (38%, right), which can have evolved from the subclone in the left.

Mentions: We defined a case indicating the same log2 ratio for all CNA as a sample without clonal heterogeneity (Fig. 1a) because the single tumor cell population was calculated from the log2 ratio(s) of all CNA in this sample. We defined a case having different log2 ratios in one sample as a sample with clonal heterogeneity (Fig. 1a). Differences in log2 ratios were evaluated using Student's t-test (P < 0.001) as previously described.(9) In a few cases, the same tumor cell population was applied when the log2 ratios were proportional at variable copy numbers (one copy gain versus two copy gain) in the same sample. For example, a log2 ratio of 0.685 indicates a tumor cell population of 61% in a case of one copy gain and 0.39 is 63% in two copy gain (Fig. S1d). We defined such a case with different log2 ratios showing one tumor cell population as a sample without clonal heterogeneity.


Clonal heterogeneity of lymphoid malignancies correlates with poor prognosis.

Suguro M, Yoshida N, Umino A, Kato H, Tagawa H, Nakagawa M, Fukuhara N, Karnan S, Takeuchi I, Hocking TD, Arita K, Karube K, Tsuzuki S, Nakamura S, Kinoshita T, Seto M - Cancer Sci. (2014)

Results of array comparative genomic hybridization (CGH) analysis for cases with and without clonal heterogeneity. (a) A case without clonal heterogeneity showing a constant log2 ratio for all copy number alterations (CNA). (Top) The result of array CGH analysis with chromosomal regions on the x-axis and log2 ratios on the y-axis. There are four CNA (arrowheads) whose log2 ratios are −0.57. (Bottom) Log2 ratio and tumor cell population. The population of tumor cells with the CNA whose log2 ratio is −0.57 is calculated as 65% (Fig. S1a–c). This case is assessed as a sample without clonal heterogeneity since populations of tumor cells with each and every CNA in this sample are the same. (b) A case with clonal heterogeneity showing different log2 ratios. (Top) The result of array CGH analysis. There are two CNA (red up arrowheads) whose log2 ratio is 0.25, five CNA (red down arrowheads) whose log2 ratios are −0.30, and two CNA (black down arrowheads) whose log2 ratios are −0.62. (Bottom left) Log2 ratios and assessed tumor cell populations. This case is assessed as a sample with clonal heterogeneity because of the different tumor cell populations. (Bottom right) The simplest model of a tumor biopsy sample with different log2 ratios explained by clonal evolution. The solid box shows a tumor biopsy sample from a patient. It consists of 30% of normal cells (30%) and 70% of tumor cells (70%, dotted box). The tumor cells consist of a subclone (32%, left) and the other subclone (38%, right), which can have evolved from the subclone in the left.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
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fig01: Results of array comparative genomic hybridization (CGH) analysis for cases with and without clonal heterogeneity. (a) A case without clonal heterogeneity showing a constant log2 ratio for all copy number alterations (CNA). (Top) The result of array CGH analysis with chromosomal regions on the x-axis and log2 ratios on the y-axis. There are four CNA (arrowheads) whose log2 ratios are −0.57. (Bottom) Log2 ratio and tumor cell population. The population of tumor cells with the CNA whose log2 ratio is −0.57 is calculated as 65% (Fig. S1a–c). This case is assessed as a sample without clonal heterogeneity since populations of tumor cells with each and every CNA in this sample are the same. (b) A case with clonal heterogeneity showing different log2 ratios. (Top) The result of array CGH analysis. There are two CNA (red up arrowheads) whose log2 ratio is 0.25, five CNA (red down arrowheads) whose log2 ratios are −0.30, and two CNA (black down arrowheads) whose log2 ratios are −0.62. (Bottom left) Log2 ratios and assessed tumor cell populations. This case is assessed as a sample with clonal heterogeneity because of the different tumor cell populations. (Bottom right) The simplest model of a tumor biopsy sample with different log2 ratios explained by clonal evolution. The solid box shows a tumor biopsy sample from a patient. It consists of 30% of normal cells (30%) and 70% of tumor cells (70%, dotted box). The tumor cells consist of a subclone (32%, left) and the other subclone (38%, right), which can have evolved from the subclone in the left.
Mentions: We defined a case indicating the same log2 ratio for all CNA as a sample without clonal heterogeneity (Fig. 1a) because the single tumor cell population was calculated from the log2 ratio(s) of all CNA in this sample. We defined a case having different log2 ratios in one sample as a sample with clonal heterogeneity (Fig. 1a). Differences in log2 ratios were evaluated using Student's t-test (P < 0.001) as previously described.(9) In a few cases, the same tumor cell population was applied when the log2 ratios were proportional at variable copy numbers (one copy gain versus two copy gain) in the same sample. For example, a log2 ratio of 0.685 indicates a tumor cell population of 61% in a case of one copy gain and 0.39 is 63% in two copy gain (Fig. S1d). We defined such a case with different log2 ratios showing one tumor cell population as a sample without clonal heterogeneity.

Bottom Line: Clonal heterogeneity in lymphoid malignancies has been recently reported in adult T-cell lymphoma/leukemia, peripheral T-cell lymphoma, not otherwise specified, and mantle cell lymphoma.To determine the presence of clonal heterogeneity, 332 cases were examined using array comparative genomic hybridization analysis.Survival analysis revealed that mantle cell lymphoma and diffuse large B-cell lymphoma with clonal heterogeneity showed significantly poorer prognosis, and that clonal heterogeneity was confirmed as an independent predictor of poor prognosis for both types of lymphoma.

View Article: PubMed Central - PubMed

Affiliation: Division of Molecular Medicine, Aichi Cancer Center Research Institute, Nagoya, Japan.

Show MeSH
Related in: MedlinePlus