Tam Michael, Lin Pei, Hu Peter, Lennon Patrick A
School of Health Professions, University of Texas at Houston, Texas.
J Assoc Genet Technol. 2010;36(3):111-4.
Mutations in genes regulating cell cycle and apoptosis are considered major culprits for the malignant transformation of cancer cells. Aberrant activation of the Hedgehog (HH) signaling pathway which primarily regulates genes involved in cell growth, proliferation, survival and apoptosis has been demonstrated in multiple myeloma. Mutations resulting in defective components of the p53 pathway, which serves a critical role in mediating cellular stress response by triggering DNA repair, cell cycle arrest, senescence and apoptosis, have also been identified. This study focuses on detecting copy number variations for the GLIPR1/GLIPR1L1/GLIPR1L2 gene cluster of the p53 pathway and three elements of the HH pathway, SHH, PTCH1 and GLI3 in multiple myeloma (MM) using fluorescence in situ hybridization (FISH). In eighteen samples, there was no evidence of abnormal copy number for PTCH1, GLI3 or SHH. Thus, it is unlikely that copy number variations of these genes are linked to multiple myeloma. However, a deletion of the GLIPR1/GLIPR1L1/ GLIPR1L2 gene cluster, all p53 targets, was found in three of 32 samples (9.4%) indicating that these deleted genes may have significant implications in MM. Further studies should be performed to determine the role of the GLIPR1/GLIPR1L1/GLIPR1L2 gene cluster in the pathogenesis of multiple myeloma.
调节细胞周期和细胞凋亡的基因突变被认为是癌细胞恶性转化的主要元凶。刺猬信号通路（HH）主要调节参与细胞生长、增殖、存活和凋亡的基因，在多发性骨髓瘤中已证实该信号通路存在异常激活。在介导细胞应激反应（通过触发DNA修复、细胞周期停滞、衰老和凋亡）中起关键作用的p53通路的缺陷成分突变也已被发现。本研究聚焦于使用荧光原位杂交（FISH）检测多发性骨髓瘤（MM）中p53通路的GLIPR1/GLIPR1L1/GLIPR1L2基因簇以及HH通路的三个元件SHH、PTCH1和GLI3的拷贝数变异。在18个样本中，没有证据表明PTCH1、GLI3或SHH存在异常拷贝数。因此，这些基因的拷贝数变异不太可能与多发性骨髓瘤相关。然而，在32个样本中的3个（9.4%）发现了GLIPR1/GLIPR1L1/GLIPR1L2基因簇（均为p53靶点）的缺失，这表明这些缺失基因可能在MM中具有重要意义。应进行进一步研究以确定GLIPR1/GLIPR1L1/GLIPR1L2基因簇在多发性骨髓瘤发病机制中的作用。
