2018
DOI: 10.1158/0008-5472.can-18-1958 View full text |Buy / Rent full text
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Abstract: Chromosomal instability (CIN) is the result of ongoing changes in the number (aneuploidy) and structure of chromosomes. CIN is induced by chromosome missegregation in mitosis and leads to karyotypic diversity within the cancer cell population, thereby adding to intratumor heterogeneity. Regardless of the overall pro-oncogenic function of CIN, its onset is typically detrimental for cell fitness and thus tumors must develop CIN-tolerance mechanisms in order to propagate. There is overwhelming genetic and functio… Show more

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“…1). This hallmark of cancer is suggested as a major modulator of tumor adaptation and evolution in response to challenges arising from the tumor microenvironment such as metastasis or therapeutic resistance (2). CIN, one of the major forms of genomic instability in various human cancers, is typically associated with structural and numerical chromosomal changes over time in tumor tissues (3)(4)(5).…”
Section: Introductionmentioning
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“…1). This hallmark of cancer is suggested as a major modulator of tumor adaptation and evolution in response to challenges arising from the tumor microenvironment such as metastasis or therapeutic resistance (2). CIN, one of the major forms of genomic instability in various human cancers, is typically associated with structural and numerical chromosomal changes over time in tumor tissues (3)(4)(5).…”
Section: Introductionmentioning
“…3) [16]. In order for tumor cells to tolerate CIN, inactivation of the TP53 gene or its associated pathway is often required [39]. Interrogation of genes linked to the hallmark p53 pathway activation signature demonstrated down-regulated in M1 relative to M0-NM tumors (p = 0.031).…”
Section: Resultsmentioning
“…A general, yet not tissue-specific, role of copy number alterations and metabolic selection pressure was reported by Graham and colleagues 25 . Of note, several publications point 7 to a reduction of cellular fitness as a consequence of general aneuploidy [26][27][28] . We show that, unlike general aneuploidy, tissue-specific aneuploidies that enhance chromosome arm-wide normal tissue-specific gene expression levels result in clonal expansion.…”
Section: Discussionmentioning