Abstract:
Different tumor types are characterized by unique histopathological patterns including distinctive nuclear architectures. I hypothesized that the difference in nuclear appearance is reflected in different nuclear maps of chromosome territories, the discrete regions occupied by individual chromosomes in the interphase nucleus. To test this hypothesis, I used interchromosomal translocations (ITLs) as an analytical tool to map chromosome territories in 11 different tumor types from the TCGA PanCancer database encompassing 6003 tumors with 5295 ITLs. For each chromosome I determined the number and percentage of all ITLs for any given tumor type. Chromosomes were ranked according to the frequency and percentage of ITLs per chromosome. The ranking showed similar patterns for all tumor types. Chromosomes 1, 8, 11, 17, and 19 were ranked in the top quarter, accounting for 35.2% of 5295 ITLs, whereas chromosomes 13, 15, 18, 21, and X were in the bottom quarter, accounting for only 10.5% ITLs. The correlation between the chromosome ranking in the total group of 6003 tumors and the ranking in individual tumor types was significant, ranging from P < .0001 to .0033. Thus, contrary to my hypothesis, different tumor types share a common nuclear map of chromosome territories. Based on the large number of ITLs in 11 different types of malignancy one can discern a shared pattern of chromosome territories in cancer and propose a probabilistic model of chromosomes 1, 8, 11, 17, 19 in the center of the nucleus and chromosomes 13, 15, 18, 21, X at the periphery.
摘要:
不同肿瘤类型的特征在于独特的组织病理学模式,包括独特的核结构。我假设核外观的差异反映在染色体区域的不同核图中,间期核中单个染色体占据的离散区域。为了检验这个假设,我使用染色体间易位(ITL)作为分析工具,从TCGAPanCancer数据库中绘制11种不同肿瘤类型的染色体区域,该数据库包含6003种肿瘤和5295个ITL。对于每个染色体,我确定了任何给定肿瘤类型的所有ITL的数量和百分比。根据每个染色体的ITL的频率和百分比对染色体进行排序。排名显示所有肿瘤类型的相似模式。染色体1、8、11、17和19排在前四分之一,占5295ITL的35.2%,而染色体13、15、18、21和X位于下四分之一,仅占10.5%的ITL。6003个肿瘤的总染色体排序与单个肿瘤类型的排序有显著的相关性,范围从P<0.0001到0.0033。因此,与我的假设相反,不同类型的肿瘤具有共同的染色体区域核图。基于11种不同类型的恶性肿瘤中的大量ITL,人们可以辨别出癌症中染色体区域的共同模式,并提出了细胞核中心的染色体1、8、11、17、19和染色体13的概率模型,15,18,21,X在外围。