Algoma District Cancer Program, Sault Area Hospital, 750 Great Northern Road, Sault Ste. Marie, ON P6B 0A8, Canada.
Section of Internal Medicine, Division of Clinical Sciences, Northern Ontario School of Medicine, Sudbury, ON P6B 0A8, Canada.
Medicina (Kaunas). 2021 Aug 24;57(9):860. doi: 10.3390/medicina57090860.
: The chromosome locus 20q11.21 is a commonly amplified locus in colorectal cancer, with a prevalence of 8% to 9%. Several candidate cancer-associated genes are transcribed from the locus. The therapeutic implications of the amplification in colorectal cancer remain unclear. : Preclinical cell line models of colorectal cancer included in the Cancer Cell Line Encyclopedia (CCLE) collection were examined for the presence of amplifications in 20q11.21 genes. Correlations of the presence of 20q11.21 amplifications with gene essentialities and drug sensitivities were surveyed on salient databases for determination of therapeutic leads. : A significant subset of colorectal cancer cell lines in the CCLE (12 of 63 cell lines, 19%) bear amplifications of genes located at 20q11.21. Cancer-associated genes of the locus include , , , , and . These genes are all amplified in the 12 cell lines, but they are variably over-expressed at the mRNA level, compared to non-amplified lines. 20q11.21 amplified cell lines are sensitive to various tyrosine kinase inhibitors and are resistant to chemotherapy drugs targeting the mitotic apparatus and microtubules. CRISPR and RNAi dependencies screening revealed, besides the β-catenin and genes, a few recurrent gene dependencies in more than one cell line, including and . : Cell line models of colorectal cancer with 20q11.21 gene amplifications display dependencies on the presence of specific genes and resistance or sensitivity to specific drugs and drug categories. Observations from in vitro models may form the basis for clinical drug development in this subtype of colorectal cancer. Genetic lesions conferring synthetic lethality to certain drugs or categories of drugs could be discovered with this approach.
: 20q11.21 染色体基因座是结直肠癌中常见的扩增基因座，其发生率为 8%至 9%。该基因座转录了几个候选癌相关基因。该扩增在结直肠癌中的治疗意义尚不清楚。 : 在癌症细胞系百科全书（Cancer Cell Line Encyclopedia，CCLE）收藏中包含的结直肠癌细胞系临床前模型中，检测了 20q11.21 基因的扩增情况。在显著的数据库中调查了 20q11.21 扩增与基因必需性和药物敏感性之间的相关性，以确定治疗线索。 : 在 CCLE 中，显著的结直肠癌细胞系亚群（63 个细胞系中的 12 个，19%）具有位于 20q11.21 的基因扩增。该基因座的癌相关基因包括、、、、和。这些基因在 12 个细胞系中均被扩增，但与非扩增细胞系相比，其 mRNA 水平的表达情况各不相同。20q11.21 扩增细胞系对各种酪氨酸激酶抑制剂敏感，对靶向有丝分裂器和微管的化疗药物耐药。CRISPR 和 RNAi 依赖性筛选显示，除了 β-连环蛋白和基因外，在多个细胞系中还存在一些反复出现的基因依赖性，包括和。 : 具有 20q11.21 基因扩增的结直肠癌细胞系模型显示出对特定基因的存在的依赖性，以及对特定药物和药物类别的耐药性或敏感性。体外模型的观察结果可能为这种结直肠癌亚型的临床药物开发奠定基础。可以通过这种方法发现赋予某些药物或药物类别合成致死性的遗传病变。
