Loss, mutation and deregulation of L3MBTL4 in breast cancers.
Loss, mutation and deregulation of L3MBTL4 in breast cancers.
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DOI：
10.1186/1476-4598-9-213
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发表时间：
2010-08-10
期刊：
影响因子：
37.3
通讯作者：
Chaffanet M
中科院分区：
文献类型：
--
作者：
Addou-Klouche L;Adélaïde J;Finetti P;Cervera N;Ferrari A;Bekhouche I;Sircoulomb F;Sotiriou C;Viens P;Moulessehoul S;Bertucci F;Birnbaum D;Chaffanet M
许多改变都与乳腺肿瘤发生有关，包括癌基因的扩增和抑癌基因（TSG）的丢失。丢失可能会影响几乎所有染色体臂，并且许多 TSG 仍有待鉴定。我们通过高分辨率阵列比较基因组杂交 (aCGH) 研究了 307 个原发性乳腺肿瘤和 47 个乳腺癌细胞系。我们确定了 18p11.31 上的一个区域在约 20% 的肿瘤和 40% 的细胞系中丢失。最小共同丢失区域 (Chr18:6,366,938-6,375,929 bp) 针对 L3MBTL4 基因。该基因也成为一种肿瘤和两种细胞系中断裂的靶标。我们研究了 180 个原发性肿瘤样本和 47 个细胞系中 L3MBTL4 的外显子序列，发现了 6 个错义和 1 个无义杂合突变。与正常乳腺组织相比，73% 的肿瘤中 L3MBTL4 mRNA 表达下调，尤其是在管腔、ERBB2 和正常样亚型中。 18p11 区域的丢失与 L3MBTL4 表达水平低相关。结合同一肿瘤的基因组和基因表达谱的综合分析指出了其他 14 个潜在的 18p TSG 候选者。 ZFP161、PPP4R1和YES1的表达下调与luminal B分子亚型相关。 ZFP161 基因低表达与不良临床结果相关。我们已将 L3MBTL4 鉴定为染色体臂 18p 的潜在 TSG。该基因是缺失、断裂和突变的靶标，其 mRNA 在乳腺肿瘤中下调。其他 18p TSG 候选者可能可以解释与乳腺肿瘤中 18p 缺失相关的侵袭性表型。
Many alterations are involved in mammary oncogenesis, including amplifications of oncogenes and losses of tumor suppressor genes (TSG). Losses may affect almost all chromosome arms and many TSGs remain to be identified. We studied 307 primary breast tumors and 47 breast cancer cell lines by high resolution array comparative genomic hybridization (aCGH). We identified a region on 18p11.31 lost in about 20% of the tumors and 40% of the cell lines. The minimal common region of loss (Chr18:6,366,938-6,375,929 bp) targeted the L3MBTL4 gene. This gene was also targeted by breakage in one tumor and in two cell lines. We studied the exon sequence of L3MBTL4 in 180 primary tumor samples and 47 cell lines and found six missense and one nonsense heterozygous mutations. Compared with normal breast tissue, L3MBTL4 mRNA expression was downregulated in 73% of the tumors notably in luminal, ERBB2 and normal-like subtypes. Losses of the 18p11 region were associated with low L3MBTL4 expression level. Integrated analysis combining genome and gene expression profiles of the same tumors pointed to 14 other potential 18p TSG candidates. Downregulated expression of ZFP161, PPP4R1 and YES1 was correlated with luminal B molecular subtype. Low ZFP161 gene expression was associated with adverse clinical outcome. We have identified L3MBTL4 as a potential TSG of chromosome arm 18p. The gene is targeted by deletion, breakage and mutations and its mRNA is downregulated in breast tumors. Additional 18p TSG candidates might explain the aggressive phenotype associated with the loss of 18p in breast tumors.
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影响因子：
16
作者：
Chowdhury, Dipanjan;Xu, Xingzhi;Zhong, Xueyan;Ahmed, Fariyal;Zhong, Jianing;Liao, Ji;Dykxhoorn, Derek M.;Weinstock, David M.;Pfeifer, Gerd P.;Lieberman, Judy
通讯作者：
Lieberman, Judy
影响因子：
14.9
作者：
Kaplan, J;Calame, K
通讯作者：
Calame, K
DOI：
10.1073/pnas.0710052104
发表时间：
2007-12-11
影响因子：
11.1
作者：
Beroukhim, Rameen;Getz, Gad;Sellers, William R.
通讯作者：
Sellers, William R.
影响因子：
30.8
作者：
Iafrate, AJ;Feuk, L;Lee, C
通讯作者：
Lee, C
影响因子：
5.8
作者：
Benito, M;Parker, J;Marron, JS
通讯作者：
Marron, JS