Definition of MYC genetic heteroclonality in diffuse large B-cell lymphoma with 8q24 rearrangement and its impact on protein expression
Definition of MYC genetic heteroclonality in diffuse large B-cell lymphoma with 8q24 rearrangement and its impact on protein expression
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8q24重排弥漫性大B细胞淋巴瘤MYC遗传异克隆性的定义及其对蛋白表达的影响
作者：
Alexandra Valera;S. Epistolio;L. Colomo;A. Riva;O. Balagué;I. Dlouhy;A. Tzankov;M. Bühler;E. Haralambieva;E. Campo;D. Soldini;L. Mazzucchelli;V. Martin
MYC重排可在预后不良的弥漫性大b细胞淋巴瘤亚组中检测到。与Burkitt淋巴瘤相比，弥漫性大b细胞淋巴瘤中MYC重排与MYC蛋白表达之间的相关性不太清楚，因为大约三分之一的重排病例免疫组化显示阴性或低表达。为了更好地了解MYC重排的特异性特征是否会影响其蛋白表达，我们通过FISH研究了43例8q24重排阳性的新生弥漫性大b细胞淋巴瘤，并使用14例Burkitt淋巴瘤进行比较。使用计算机图像系统检测和分析不同的细胞群（克隆）、断点（经典与非经典FISH模式）、伴侣基因（IGH与非IGH）和免疫染色。在弥漫性大b细胞淋巴瘤亚组中，我们观察到同一肿瘤内的不同克隆，将MYC重排的创始克隆与其他亚克隆区分开来，这些亚克隆携带MYC重排，并伴有衍生物/正常等位基因的丢失/额外拷贝。这张图被我们定义为MYC遗传异克隆，在42%的病例中发现，与MYC阴性表达相关（P=0.026）。在16%的弥漫性大b细胞淋巴瘤中检测到非经典FISH断点，但不影响表达（P=0.040）。非igh基因是弥散性大b细胞淋巴瘤MYC异克隆（P=0.016）和/或非经典FISH断点（P=0.058）重排的优先伴侣。在Burkitt淋巴瘤中未观察到MYC异克隆性，所有病例均有MYC阳性表达。非经典FISH MYC断点和非igh伴侣分别在29%和20%的伯基特淋巴瘤中被发现。总之，MYC基因异克隆性在弥漫性大b细胞淋巴瘤中是一个常见的事件，可能在调节MYC表达中起相关作用。
MYC rearrangement can be detected in a subgroup of diffuse large B-cell lymphoma characterized by unfavorable prognosis. In contrast to Burkitt lymphoma, the correlation between MYC rearrangement and MYC protein expression in diffuse large B-cell lymphoma is less clear, as approximately one-third of rearranged cases show negative or low expression by immunohistochemistry. To better understand whether specific characteristics of the MYC rearrangement may influence its protein expression, we investigated 43 de novo diffuse large B-cell lymphoma positive for 8q24 rearrangement by FISH, using 14 Burkitt lymphoma for comparison. Different cell populations (clones), breakpoints (classical vs non-classical FISH patterns), partner genes (IGH vs non-IGH) and immunostaining were detected and analyzed using computerized image systems. In a subgroup of diffuse large B-cell lymphoma, we observed different clones within the same tumor distinguishing the founder clone with MYC rearrangement alone from other subclones, carrying MYC rearrangement coupled with loss/extra copies of derivatives/normal alleles. This picture, which we defined MYC genetic heteroclonality, was found in 42% of cases and correlated to negative MYC expression (P=0.026). Non-classical FISH breakpoints were detected in 16% of diffuse large B-cell lymphoma without affecting expression (P=0.040). Non-IGH gene was the preferential partner of rearrangement in those diffuse large B-cell lymphoma showing MYC heteroclonality (P=0.016) and/or non-classical FISH breakpoints (P=0.058). MYC heteroclonality was not observed in Burkitt lymphoma and all cases had positive MYC expression. Non-classical FISH MYC breakpoint and non-IGH partner were found in 29 and 20% of Burkitt lymphoma, respectively. In conclusion, MYC genetic heteroclonality is a frequent event in diffuse large B-cell lymphoma and may have a relevant role in modulating MYC expression.
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弥漫性大细胞淋巴瘤中涉及 8q24 条带的 MYC 重排和易位。
影响因子：
20.3
作者：
Ladanyi,M;Offit,K;Jhanwar,SC;Filippa,DA;Chaganti,RS
通讯作者：
Chaganti,RS
DOI：
10.1073/pnas.83.9.2984
发表时间：
1986-05-01
影响因子：
11.1
作者：
PELICCI, PG;KNOWLES, DM;DALLAFAVERA, R
通讯作者：
DALLAFAVERA, R
影响因子：
20.3
作者：
Hans, CP;Weisenburger, DD;Chan, WC
通讯作者：
Chan, WC
影响因子：
20.3
作者：
Johnson, Nathalie A.;Savage, Kerry J.;Horsman, Douglas E.
通讯作者：
Horsman, Douglas E.
影响因子：
10.1
作者：
Aukema, Sietse M.;Kreuz, Markus;Siebert, Reiner
通讯作者：
Siebert, Reiner