Limits...
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.

Show MeSH

Related in: MedlinePlus

(a) Genome-wide frequency of the genomic imbalance in diffuse large B-cell lymphoma (DLBCL) subtypes: non-germinal center B-cell-like (GCB) group (26 cases) and GCB group (20 cases). Horizontal lines indicate 2213 BAC/PAC clones ordered from chromosomes 1 to 22 and X. Within each chromosome, clones are shown in order from the p telomere to the q telomere. Vertical lines indicate the frequency (%) of gains and losses. Non-GCB and GCB subtypes are shown to have different genomic imbalance characteristics. (b) Contrastive analysis of genomic gains of GCB and non-GCB subtypes with frequencies of >50%. Horizontal lines indicate BAC/PAC clones of genomic gains with high frequencies (>50%) in each subtype in order of increasing frequencies of gains in the GCB subtype. Vertical lines indicate the frequency (%) of gains. The figure shows that the frequencies of gains at specific loci in each subtype were different. (c) Contrastive analysis of genomic losses of GCB and non-GCB subtypes with frequencies of >40%. Horizontal lines indicate BAC/PAC clones of genomic losses with high frequencies (>40%) in each subtype in order of increasing frequency of losses in GCB samples. Vertical lines indicate the frequency (%) of losses. The frequencies of genomic losses with high frequencies (>40%) were different between the non-GCB and GCB subtypes.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4317812&req=5

fig03: (a) Genome-wide frequency of the genomic imbalance in diffuse large B-cell lymphoma (DLBCL) subtypes: non-germinal center B-cell-like (GCB) group (26 cases) and GCB group (20 cases). Horizontal lines indicate 2213 BAC/PAC clones ordered from chromosomes 1 to 22 and X. Within each chromosome, clones are shown in order from the p telomere to the q telomere. Vertical lines indicate the frequency (%) of gains and losses. Non-GCB and GCB subtypes are shown to have different genomic imbalance characteristics. (b) Contrastive analysis of genomic gains of GCB and non-GCB subtypes with frequencies of >50%. Horizontal lines indicate BAC/PAC clones of genomic gains with high frequencies (>50%) in each subtype in order of increasing frequencies of gains in the GCB subtype. Vertical lines indicate the frequency (%) of gains. The figure shows that the frequencies of gains at specific loci in each subtype were different. (c) Contrastive analysis of genomic losses of GCB and non-GCB subtypes with frequencies of >40%. Horizontal lines indicate BAC/PAC clones of genomic losses with high frequencies (>40%) in each subtype in order of increasing frequency of losses in GCB samples. Vertical lines indicate the frequency (%) of losses. The frequencies of genomic losses with high frequencies (>40%) were different between the non-GCB and GCB subtypes.

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)

(a) Genome-wide frequency of the genomic imbalance in diffuse large B-cell lymphoma (DLBCL) subtypes: non-germinal center B-cell-like (GCB) group (26 cases) and GCB group (20 cases). Horizontal lines indicate 2213 BAC/PAC clones ordered from chromosomes 1 to 22 and X. Within each chromosome, clones are shown in order from the p telomere to the q telomere. Vertical lines indicate the frequency (%) of gains and losses. Non-GCB and GCB subtypes are shown to have different genomic imbalance characteristics. (b) Contrastive analysis of genomic gains of GCB and non-GCB subtypes with frequencies of >50%. Horizontal lines indicate BAC/PAC clones of genomic gains with high frequencies (>50%) in each subtype in order of increasing frequencies of gains in the GCB subtype. Vertical lines indicate the frequency (%) of gains. The figure shows that the frequencies of gains at specific loci in each subtype were different. (c) Contrastive analysis of genomic losses of GCB and non-GCB subtypes with frequencies of >40%. Horizontal lines indicate BAC/PAC clones of genomic losses with high frequencies (>40%) in each subtype in order of increasing frequency of losses in GCB samples. Vertical lines indicate the frequency (%) of losses. The frequencies of genomic losses with high frequencies (>40%) were different between the non-GCB and GCB subtypes.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig03: (a) Genome-wide frequency of the genomic imbalance in diffuse large B-cell lymphoma (DLBCL) subtypes: non-germinal center B-cell-like (GCB) group (26 cases) and GCB group (20 cases). Horizontal lines indicate 2213 BAC/PAC clones ordered from chromosomes 1 to 22 and X. Within each chromosome, clones are shown in order from the p telomere to the q telomere. Vertical lines indicate the frequency (%) of gains and losses. Non-GCB and GCB subtypes are shown to have different genomic imbalance characteristics. (b) Contrastive analysis of genomic gains of GCB and non-GCB subtypes with frequencies of >50%. Horizontal lines indicate BAC/PAC clones of genomic gains with high frequencies (>50%) in each subtype in order of increasing frequencies of gains in the GCB subtype. Vertical lines indicate the frequency (%) of gains. The figure shows that the frequencies of gains at specific loci in each subtype were different. (c) Contrastive analysis of genomic losses of GCB and non-GCB subtypes with frequencies of >40%. Horizontal lines indicate BAC/PAC clones of genomic losses with high frequencies (>40%) in each subtype in order of increasing frequency of losses in GCB samples. Vertical lines indicate the frequency (%) of losses. The frequencies of genomic losses with high frequencies (>40%) were different between the non-GCB and GCB subtypes.
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