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Array-comparative genomic hybridization profiling of immunohistochemical subgroups of diffuse large B-cell lymphoma shows distinct genomic alterations.

Guo Y, Takeuchi I, Karnan S, Miyata T, Ohshima K, Seto M - Cancer Sci. (2014)

Bottom Line: The GCB type was characterized by more gains at 7q (7q22.1, P < 0.05) and losses at 16q (P ≤ 0.05), while the non-GCB type was characterized by gains at 11q24.3 and 3q13.2 (P < 0.05).The BCL6- group had a higher frequency of genomic imbalances compared to the BCL6+ group.In conclusion, the BCL6+ and BCL6- non-GCB type of DLBCL appear to have different mechanisms of pathogenesis.

View Article: PubMed Central - PubMed

ABSTRACT
Diffuse large B-cell lymphoma (DLBCL) displays striking heterogeneity at the clinical, genetic and molecular levels. Subtypes include germinal center B-cell-like (GCB) DLBCL and activated B-cell-like (ABC) DLBCL, according to microarray analysis, and germinal center type or non-germinal center type by immunohistochemistry. Although some reports have described genomic aberrations based upon microarray classification system, genomic aberrations based upon immunohistochemical classifications have rarely been reported. The present study aimed to ascertain the relationship between genomic aberrations and subtypes identified by immunohistochemistry, and to study the pathogenetic character of Chinese DLBCL. We conducted immunohistochemistry using antibodies against CD10, BCL6 and MUM1 in 59 samples of DLBCL from Chinese patients, and then performed microarray-based comparative genomic hybridization for each case. Characteristic genomic differences were found between GCB and non-GCB DLBCL from the array data. The GCB type was characterized by more gains at 7q (7q22.1, P < 0.05) and losses at 16q (P ≤ 0.05), while the non-GCB type was characterized by gains at 11q24.3 and 3q13.2 (P < 0.05). We found completely different mutations in BCL6+ and BCL6- non-GCB type DLBCL, whereby the BCL6- group had a higher number of gains at 1q and a loss at 14q32.13 (P ≤ 0.005), while the BCL6+ group showed a higher number of gains at 14q23.1 (P = 0.15) and losses at 6q (P = 0.07). The BCL6- group had a higher frequency of genomic imbalances compared to the BCL6+ group. In conclusion, the BCL6+ and BCL6- non-GCB type of DLBCL appear to have different mechanisms of pathogenesis.

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Representative array CGH profile of germinal center B-cell-like (GCB) and non-GCB diffuse large B cell lymphomas. Log2 ratios for all clones were plotted based on their chromosome position, with the vertical dotted bars representing the separation of chromosomes. Clones are ordered from chromosome 1 to 22 followed by X. The upper figure shows gain of 7q in a case of GCB diffuse large B-cell lymphoma (DLBCL). The lower figure shows a gain of 1q and a loss of 6q in a case of non-GCB DLBCL.
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fig02: Representative array CGH profile of germinal center B-cell-like (GCB) and non-GCB diffuse large B cell lymphomas. Log2 ratios for all clones were plotted based on their chromosome position, with the vertical dotted bars representing the separation of chromosomes. Clones are ordered from chromosome 1 to 22 followed by X. The upper figure shows gain of 7q in a case of GCB diffuse large B-cell lymphoma (DLBCL). The lower figure shows a gain of 1q and a loss of 6q in a case of non-GCB DLBCL.

Mentions: Array CGH was successfully performed on 46 of the 59 DLBCL cases. Gains at 1q, 2p, 3q, 7, 11q, 12q, 17q and 18q, and losses at 1p, 2q, 6q, 8p and 16q were frequent (>40%) genomic aberrations among the Chinese DLBCL patients. Frequent genomic imbalances (copy number changes) in the non-GCB subtype were gains (>40%) at 1q, 3q, 6p21, 7q22–31.1, 9p24.1, 11q24, 12q, 17q21.1 and 18q and losses (>40%) at 1p36, 1q43, 6q, 8p21, 8q24, 10q, 15q11.2 and 16q12.2. Frequent genomic imbalances in the GCB subtype (>40%) were gains at 1q23, 2p16.1, 3q29, 6p21–23, 7, 8q24, 11q13.4, 11q22–q24, 12q15, 12q21–q24, 14q23.1, 16p13.3, 17q21.2, 17q24.1 and 21q22.1 and losses at 1p36.32, 2q14, 4p15.31, 6q and 16q. The non-GCB subtype was genomically characterized by more frequent gains at 11q24.3 and 3q13.2 (P < 0.05). The GCB group was genomically characterized by more frequent gains at 7q (7q22.1, P < 0.05), and losses at 16q (P < 0.05) (Figs 2and 3a–c, Table 3).


Array-comparative genomic hybridization profiling of immunohistochemical subgroups of diffuse large B-cell lymphoma shows distinct genomic alterations.

Guo Y, Takeuchi I, Karnan S, Miyata T, Ohshima K, Seto M - Cancer Sci. (2014)

Representative array CGH profile of germinal center B-cell-like (GCB) and non-GCB diffuse large B cell lymphomas. Log2 ratios for all clones were plotted based on their chromosome position, with the vertical dotted bars representing the separation of chromosomes. Clones are ordered from chromosome 1 to 22 followed by X. The upper figure shows gain of 7q in a case of GCB diffuse large B-cell lymphoma (DLBCL). The lower figure shows a gain of 1q and a loss of 6q in a case of non-GCB DLBCL.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4317812&req=5

fig02: Representative array CGH profile of germinal center B-cell-like (GCB) and non-GCB diffuse large B cell lymphomas. Log2 ratios for all clones were plotted based on their chromosome position, with the vertical dotted bars representing the separation of chromosomes. Clones are ordered from chromosome 1 to 22 followed by X. The upper figure shows gain of 7q in a case of GCB diffuse large B-cell lymphoma (DLBCL). The lower figure shows a gain of 1q and a loss of 6q in a case of non-GCB DLBCL.
Mentions: Array CGH was successfully performed on 46 of the 59 DLBCL cases. Gains at 1q, 2p, 3q, 7, 11q, 12q, 17q and 18q, and losses at 1p, 2q, 6q, 8p and 16q were frequent (>40%) genomic aberrations among the Chinese DLBCL patients. Frequent genomic imbalances (copy number changes) in the non-GCB subtype were gains (>40%) at 1q, 3q, 6p21, 7q22–31.1, 9p24.1, 11q24, 12q, 17q21.1 and 18q and losses (>40%) at 1p36, 1q43, 6q, 8p21, 8q24, 10q, 15q11.2 and 16q12.2. Frequent genomic imbalances in the GCB subtype (>40%) were gains at 1q23, 2p16.1, 3q29, 6p21–23, 7, 8q24, 11q13.4, 11q22–q24, 12q15, 12q21–q24, 14q23.1, 16p13.3, 17q21.2, 17q24.1 and 21q22.1 and losses at 1p36.32, 2q14, 4p15.31, 6q and 16q. The non-GCB subtype was genomically characterized by more frequent gains at 11q24.3 and 3q13.2 (P < 0.05). The GCB group was genomically characterized by more frequent gains at 7q (7q22.1, P < 0.05), and losses at 16q (P < 0.05) (Figs 2and 3a–c, Table 3).

Bottom Line: The GCB type was characterized by more gains at 7q (7q22.1, P < 0.05) and losses at 16q (P ≤ 0.05), while the non-GCB type was characterized by gains at 11q24.3 and 3q13.2 (P < 0.05).The BCL6- group had a higher frequency of genomic imbalances compared to the BCL6+ group.In conclusion, the BCL6+ and BCL6- non-GCB type of DLBCL appear to have different mechanisms of pathogenesis.

View Article: PubMed Central - PubMed

ABSTRACT
Diffuse large B-cell lymphoma (DLBCL) displays striking heterogeneity at the clinical, genetic and molecular levels. Subtypes include germinal center B-cell-like (GCB) DLBCL and activated B-cell-like (ABC) DLBCL, according to microarray analysis, and germinal center type or non-germinal center type by immunohistochemistry. Although some reports have described genomic aberrations based upon microarray classification system, genomic aberrations based upon immunohistochemical classifications have rarely been reported. The present study aimed to ascertain the relationship between genomic aberrations and subtypes identified by immunohistochemistry, and to study the pathogenetic character of Chinese DLBCL. We conducted immunohistochemistry using antibodies against CD10, BCL6 and MUM1 in 59 samples of DLBCL from Chinese patients, and then performed microarray-based comparative genomic hybridization for each case. Characteristic genomic differences were found between GCB and non-GCB DLBCL from the array data. The GCB type was characterized by more gains at 7q (7q22.1, P < 0.05) and losses at 16q (P ≤ 0.05), while the non-GCB type was characterized by gains at 11q24.3 and 3q13.2 (P < 0.05). We found completely different mutations in BCL6+ and BCL6- non-GCB type DLBCL, whereby the BCL6- group had a higher number of gains at 1q and a loss at 14q32.13 (P ≤ 0.005), while the BCL6+ group showed a higher number of gains at 14q23.1 (P = 0.15) and losses at 6q (P = 0.07). The BCL6- group had a higher frequency of genomic imbalances compared to the BCL6+ group. In conclusion, the BCL6+ and BCL6- non-GCB type of DLBCL appear to have different mechanisms of pathogenesis.

Show MeSH
Related in: MedlinePlus