b'Section 1: Molecular mechanisms of cancerExploring molecular mechanisms of malignancy gene mutations. This study revealed that the combination of both The promise of precision medicine and personalized cancertypes of mutations activated inflammation and growth factor treatments is deeply rooted in building a deeper understandingpathways, which may contribute to malignancy. The authors of the molecular mechanisms that differentiate cancer onset,suggested that inhibition of mutant p53 GOF or suppression progression, and metastasis across cancer types and individualof TP53 LOH might present opportunities for preventing CRC patients. Genetic mutations and epigenetic modifications aremetastasis [3].inextricably linked. Gene mutations can disrupt epigenetic mechanisms, and epigenetic modifications can drive genomeEpigenetic mechanisms instability and mutagenesis [1]. Here, we discuss the cellularApproximately 1015% of colorectal cancers (CRCs) have a high mechanisms involved in cancer development and thefrequency of mutation in repetitive DNA sequences, referred contributions of genetic analysis technologies in furtheringto as microsatellite instability (MSI), which is thought to result our understanding. primarily from mismatch repair (MMR) defects. Hypermethylation of promoter regions can be one cause of MMR defects. DNA Genetic mechanismsmethylation, microRNA overexpression, and histone modification Sanger sequencing and Applied Biosystems TaqMan qPCRare all epigenetic modifications that can cause gene expression assays are gold-standard approaches to detecting, identifying,changes that have been implicated in carcinogenesis and and quantifying expression of mutated genes to reveal possiblecancer progression [4-6]. Cells that are MMR-deficient usually mechanisms of cancer progression. One mechanism is oxygenhave many mutations, which may also lead to cancer. However, deprivation, which stimulates vascularization of solid tumorsin sporadic cancers, mutations in repair genes themselves are and promotes cell mobility. Islam et al. used Sanger sequencingrarely the cause of MMR deficiency. Inhibition of DNA repair and TaqMan Assays (qPCR) together to investigate possiblegenes by epigenetic events is a more likely cause. Sequencing impacts of genetic mutations on oxygen availability in the tumorand expression analysis are fundamental to revealing genes that microenvironment in adrenal gland cancers, and subsequentare impacted by epigenetic mechanisms and their roles in cancer implications for metastasis. Using Sanger sequencing by capillaryprogression. Studies using Sanger sequencing have identified electrophoresis, they identified multiple copy number mutationsmutations that indicated that most sporadic CRCs with high in an endothelial signaling protein gene, EPAS1, which is inducedMSI originated from somatic MMR mutations [4,7]. Therapies by hypoxia and is implicated in many cancers. The copy numberthat modify epigenetic patterns are leading to new research changes were then correlated with EPAS1 mRNA overexpressionapproaches for some cancers [1]. by qPCR to measure gene expression. The amplification andMicroRNA (miRNA) dysregulation is another epigenetic cause of expression mutations were associated with tumor location,MMR deficiency that is associated with carcinogenesis, malignant suggesting a role in carcinogenesis and metastasis as well astransformation, and metastasis in multiple types of cancers. potential for predicting disease progression [2].When overexpressed, miRNA bound to mRNA can cause the Genotyping with TaqMan Assays is a powerful approach tomRNA to degrade or be poorly translated [8]. Although the associate genetic mutations with alterations in cancer-relatedcanonical targets of miRNAs are noncoding promoter regions, pathways and cancer cell behavior. For example, TP53 missenserecent evidence suggests that miRNAs can bind to sites within mutations are the most frequent gene mutations across all humancoding sequences as well. Binding of miRNA within coding cancers. They result in protein gain of function (GOF), which issequences may be implicated in some cancers. A recent study implicated in cancer progression and malignancy. In addition,revealed a missense mutation within the coding sequence of loss of wild type TP53 through loss of heterozygosity (LOH) isan adult-type granulosa cell tumor (AGCT) suppressor gene. found in more than 93% of human cancers. GOF mutations areThe gene mutation provided a target site for a miRNA mutation. often found together with LOH mutations in metastatic cancers.Subsequent binding of the miRNA resulted in degradation of the In colorectal cancer (CRC), for example, LOH in wild type TP53tumor suppressor mRNA and haploinsufficiency of the tumor and mutant p53 GOF are both required for metastasis. However,suppressor itself. miRNA expression analysis using TaqMan little is known about how they cooperate to promote malignantAssays revealed that abundance of the miRNA mutation and the progression. To investigate this mechanism, Nakayama et al.tumor suppressor variant were highly correlated with malignancy. genotyped organoid cell lines by SNP genotyping using TaqManThe authors suggested that this missense mutation may provide Assays to explore GOFLOH relationships in different CRC drivera promising therapeutic target and prognostic parameter for patients with AGCT [9]. Contents 3'