Heteroplasmy and Copy Number Variations of Mitochondria in 88 Hepatocellular Carcinoma Individuals

Mitochondria are organelles that perform major roles in cellular operation. Thus, alterations in mitochondrial genome (mtGenome) may lead to mitochondrial dysfunction and cellular deregulation, influencing carcinogenesis. Gastric cancer (GC) is one of the most incident and mortal types of cancer in Brazil, particularly in the Amazon region. Here, we sequenced and compared the whole mtGenome extracted from FFPE tissue samples of GC patients (tumor and internal control – IC) and cancer-free individuals (external control – EC) from this region. We found 3-fold more variants and up to 9-fold more heteroplasmic regions in tumor when compared to paired IC samples. Moreover, tumor presented more heteroplasmic variants when compared to EC, while IC and EC showed no significant difference when compared to each other. Tumor also presented substantially more variants in the following regions: MT-RNR1, MT-ND5, MT-ND4, MT-ND2, MT-DLOOP1 and MT-CO1. In addition, our haplogroup results indicate an association of Native American ancestry (particularly haplogroup C) to gastric cancer development. To the best of our knowledge, this is the first study to sequence the whole mtGenome from FFPE samples and to apply mtGenome analysis in association to GC in Brazil.

Section: Discussionmentioning

confidence: 95%

Whole mitochondrial genome sequencing highlights mitochondrial impact in gastric cancer

Cavalcante

Marinho

Anaissi

et al. 2019

“…MTND6 provides a quinone binding sites and is one of the six subunits ( ND1-ND6 ) of the complex I in electron transport chain (ETS) in mitochondria. Mutations in MTND6 are associated with an increase in metastatic potential that was associated with low NADH and high reactive oxygen species (ROS) in lung and breast cancer cell lines 65 , 66 and heptatocellular carcinoma 67 . Mutation in one of the subunits of ETS leads to low oxidative phosphorylation and increased glycolytic activity of mitochondria contributing to aggressiveness of childhood Acute Lymphoblastic Leukemia 68 .…”

Section: Discussionmentioning

confidence: 99%

Genome-wide methylation analyses identifies Non-coding RNA genes dysregulated in breast tumours that metastasise to the brain

Pangeni

Olivaries

Huen

et al. 2022

Brain metastases comprise 40% of all metastatic tumours and breast tumours are among the tumours that most commonly metastasise to the brain, the role that epigenetic gene dysregulation plays in this process is not well understood. We carried out 450 K methylation array analysis to investigate epigenetically dysregulated genes in breast to brain metastases (BBM) compared to normal breast tissues (BN) and primary breast tumours (BP). For this, we referenced 450 K methylation data for BBM tumours prepared in our laboratory with BN and BP from The Cancer Genome Atlas. Experimental validation on our initially identified genes, in an independent cohort of BP and in BBM and their originating primary breast tumours using Combined Bisulphite and Restriction Analysis (CoBRA) and Methylation Specific PCR identified three genes (RP11-713P17.4, MIR124-2, NUS1P3) that are hypermethylated and three genes (MIR3193, CTD-2023M8.1 and MTND6P4) that are hypomethylated in breast to brain metastases. In addition, methylation differences in candidate genes between BBM tumours and originating primary tumours shows dysregulation of DNA methylation occurs either at an early stage of tumour evolution (in the primary tumour) or at a later evolutionary stage (where the epigenetic change is only observed in the brain metastasis). Epigentic changes identified could also be found when analysing tumour free circulating DNA (tfcDNA) in patient’s serum taken during BBM biopsies. Epigenetic dysregulation of RP11-713P17.4, MIR3193, MTND6P4 are early events suggesting a potential use for these genes as prognostic markers.

“…The different expression of lncRNAs in colorectal cancer indicate that lncRNAs are involved in all stages of colorectal cancer. In colorectal cancer pathogenesis, lncRNAs are implicated in a variety of signaling pathways including the Wnt/-catenin signaling pathway, epidermal growth factor receptor (EGFR)/insulin-like growth factor type I receptor (IGF-IR) signaling pathway, KRAS and phosphatidylinositol-3-kinase (PI3K) pathways, transforming growth factor-beta (TGF-) signaling pathway, p53 signaling pathway, and the epithelial-mesenchymal transition (EMT) pathway 31 . While it is still unclear how STXBP5-AS1 contributes to colon carcinogenesis, in a study involving 1067 breast cancer samples, Guo et al identified STXBP5-AS1 among lncRNA genes which play a role in predicting the prognostic survival with good sensitivity and specificity.…”

Section: Discussionmentioning

confidence: 99%

Genetic risk factors for colorectal cancer in multiethnic Indonesians

Yusuf

Pardamean

Baurley

et al. 2021

Colorectal cancer is a common cancer in Indonesia, yet it has been understudied in this resource-constrained setting. We conducted a genome-wide association study focused on evaluation and preliminary discovery of colorectal cancer risk factors in Indonesians. We administered detailed questionnaires and collecting blood samples from 162 colorectal cancer cases throughout Makassar, Indonesia. We also established a control set of 193 healthy individuals frequency matched by age, sex, and ethnicity. A genome-wide association analysis was performed on 84 cases and 89 controls passing quality control. We evaluated known colorectal cancer genetic variants using logistic regression and established a genome-wide polygenic risk model using a Bayesian variable selection technique. We replicate associations for rs9497673, rs6936461 and rs7758229 on chromosome 6; rs11255841 on chromosome 10; and rs4779584, rs11632715, and rs73376930 on chromosome 15. Polygenic modeling identified 10 SNP associated with colorectal cancer risk. This work helps characterize the relationship between variants in the SCL22A3, SCG5, GREM1, and STXBP5-AS1 genes and colorectal cancer in a diverse Indonesian population. With further biobanking and international research collaborations, variants specific to colorectal cancer risk in Indonesians will be identified.