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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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Chromosomal regions and frequencies of copy number alterations (CNA) for DLBCL with and without clonal heterogeneity. (a) CNA for 55 diffuse large B-cell lymphoma (DLBCL) cases with clonal heterogeneity. The x-axis represents chromosomal regions and the y-axis represents frequencies of gain (above 0) or loss (below 0). (b) CNA for 62 DLBCL cases without clonal heterogeneity. The profile of cases without clonal heterogeneity resembles those of cases with clonal heterogeneity (a) while loss of 9p and 17p are less common in cases without heterogeneity than in those with (arrowheads). (c) Differences in CNA between DLBCL with and without clonal heterogeneity. (Top) Subtraction of frequencies of gain in cases without clonal heterogeneity (b, red area) from those with (a, red area). The y-axis represents differences in frequency (>0: higher frequencies in cases with clonal heterogeneity; <0: higher frequencies in those without clonal heterogeneity). The characteristic gain in DLBCL cases with clonal heterogeneity is 19p (arrowhead) with more than 25% differences between cases with and without clonal heterogeneity. (Bottom) Subtraction of frequencies of loss in cases without clonal heterogeneity (b, blue area) from those with clonal heterogeneity (a, blue area). The y-axis represents differences (>0: higher frequencies in cases with clonal heterogeneity; <0: higher frequencies in those without clonal heterogeneity). The characteristic loss in DLBCL cases with clonal heterogeneity are 9p and 17p (arrow heads). All gain and loss with differences >25% are summarized in Table 3.
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fig02: Chromosomal regions and frequencies of copy number alterations (CNA) for DLBCL with and without clonal heterogeneity. (a) CNA for 55 diffuse large B-cell lymphoma (DLBCL) cases with clonal heterogeneity. The x-axis represents chromosomal regions and the y-axis represents frequencies of gain (above 0) or loss (below 0). (b) CNA for 62 DLBCL cases without clonal heterogeneity. The profile of cases without clonal heterogeneity resembles those of cases with clonal heterogeneity (a) while loss of 9p and 17p are less common in cases without heterogeneity than in those with (arrowheads). (c) Differences in CNA between DLBCL with and without clonal heterogeneity. (Top) Subtraction of frequencies of gain in cases without clonal heterogeneity (b, red area) from those with (a, red area). The y-axis represents differences in frequency (>0: higher frequencies in cases with clonal heterogeneity; <0: higher frequencies in those without clonal heterogeneity). The characteristic gain in DLBCL cases with clonal heterogeneity is 19p (arrowhead) with more than 25% differences between cases with and without clonal heterogeneity. (Bottom) Subtraction of frequencies of loss in cases without clonal heterogeneity (b, blue area) from those with clonal heterogeneity (a, blue area). The y-axis represents differences (>0: higher frequencies in cases with clonal heterogeneity; <0: higher frequencies in those without clonal heterogeneity). The characteristic loss in DLBCL cases with clonal heterogeneity are 9p and 17p (arrow heads). All gain and loss with differences >25% are summarized in Table 3.

Mentions: Chromosomal regions and frequencies of CNA were compared between cases with and without clonal heterogeneity (Fig. 2, Fig. S2–7; Table 3). Recurrent CNA among various types of lymphoma with clonal heterogeneity were found to be 8q24.1 (minimal overlapping lesion: MYC) gain, 9p21.3 (CDKN2A/2B) loss and 17p13 (TP53, ATP1B2, SAT2, SHBG) loss. The 8p24.1 (MYC) gain was found in significantly more cases with clonal heterogeneity than in those without clonal heterogeneity in follicular lymphoma and PTCL-NOS. The 9p21.3 loss was found in mantle cell lymphoma, DLBCL and PTCL-NOS. The 17p13 loss was found in mantle cell lymphoma, DLBCL, Burkitt lymphoma and PTCL-NOS (Fig. 3).


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)

Chromosomal regions and frequencies of copy number alterations (CNA) for DLBCL with and without clonal heterogeneity. (a) CNA for 55 diffuse large B-cell lymphoma (DLBCL) cases with clonal heterogeneity. The x-axis represents chromosomal regions and the y-axis represents frequencies of gain (above 0) or loss (below 0). (b) CNA for 62 DLBCL cases without clonal heterogeneity. The profile of cases without clonal heterogeneity resembles those of cases with clonal heterogeneity (a) while loss of 9p and 17p are less common in cases without heterogeneity than in those with (arrowheads). (c) Differences in CNA between DLBCL with and without clonal heterogeneity. (Top) Subtraction of frequencies of gain in cases without clonal heterogeneity (b, red area) from those with (a, red area). The y-axis represents differences in frequency (>0: higher frequencies in cases with clonal heterogeneity; <0: higher frequencies in those without clonal heterogeneity). The characteristic gain in DLBCL cases with clonal heterogeneity is 19p (arrowhead) with more than 25% differences between cases with and without clonal heterogeneity. (Bottom) Subtraction of frequencies of loss in cases without clonal heterogeneity (b, blue area) from those with clonal heterogeneity (a, blue area). The y-axis represents differences (>0: higher frequencies in cases with clonal heterogeneity; <0: higher frequencies in those without clonal heterogeneity). The characteristic loss in DLBCL cases with clonal heterogeneity are 9p and 17p (arrow heads). All gain and loss with differences >25% are summarized in Table 3.
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fig02: Chromosomal regions and frequencies of copy number alterations (CNA) for DLBCL with and without clonal heterogeneity. (a) CNA for 55 diffuse large B-cell lymphoma (DLBCL) cases with clonal heterogeneity. The x-axis represents chromosomal regions and the y-axis represents frequencies of gain (above 0) or loss (below 0). (b) CNA for 62 DLBCL cases without clonal heterogeneity. The profile of cases without clonal heterogeneity resembles those of cases with clonal heterogeneity (a) while loss of 9p and 17p are less common in cases without heterogeneity than in those with (arrowheads). (c) Differences in CNA between DLBCL with and without clonal heterogeneity. (Top) Subtraction of frequencies of gain in cases without clonal heterogeneity (b, red area) from those with (a, red area). The y-axis represents differences in frequency (>0: higher frequencies in cases with clonal heterogeneity; <0: higher frequencies in those without clonal heterogeneity). The characteristic gain in DLBCL cases with clonal heterogeneity is 19p (arrowhead) with more than 25% differences between cases with and without clonal heterogeneity. (Bottom) Subtraction of frequencies of loss in cases without clonal heterogeneity (b, blue area) from those with clonal heterogeneity (a, blue area). The y-axis represents differences (>0: higher frequencies in cases with clonal heterogeneity; <0: higher frequencies in those without clonal heterogeneity). The characteristic loss in DLBCL cases with clonal heterogeneity are 9p and 17p (arrow heads). All gain and loss with differences >25% are summarized in Table 3.
Mentions: Chromosomal regions and frequencies of CNA were compared between cases with and without clonal heterogeneity (Fig. 2, Fig. S2–7; Table 3). Recurrent CNA among various types of lymphoma with clonal heterogeneity were found to be 8q24.1 (minimal overlapping lesion: MYC) gain, 9p21.3 (CDKN2A/2B) loss and 17p13 (TP53, ATP1B2, SAT2, SHBG) loss. The 8p24.1 (MYC) gain was found in significantly more cases with clonal heterogeneity than in those without clonal heterogeneity in follicular lymphoma and PTCL-NOS. The 9p21.3 loss was found in mantle cell lymphoma, DLBCL and PTCL-NOS. The 17p13 loss was found in mantle cell lymphoma, DLBCL, Burkitt lymphoma and PTCL-NOS (Fig. 3).

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