Project description:Spontaneously occurring canine mammary cancer (MC) represents an excellent model of human breast cancer, but is greatly understudied. We performed high density arrays on 12 canine MC cases, including 7 simple carcinomas and four complex carcinomas. Simple carcinomas, which histologically match human breast carcinomas, harbor extensive genomic aberrations, many faithfully recapitulating key features of human breast cancer. Complex carcinomas, with luminal and myoepithelial cells both proliferating (which is rare in human breast cancer), appear to lack genomic abnormalities. Comparison of CNAs from canine mammary simple carcinomas and complex carcinomas
Project description:Peptide yield was enhanced through copy number amplification, and the resulting mCherry–GLP-1(9–37) can be directly used—following enterokinase cleavage—as a chemical precursor for semaglutide synthesis.
Project description:Many studies have shown that primary prostate cancers are multifocal1-3, and are composed of multiple genetically distinct cancer cell clones4-6. Whether or not multiclonal primary prostate cancers typically give rise to multiclonal or monoclonal prostate cancer metastases is largely unknown, although studies at single chromosomal loci are consistent with the latter. Here we show through a high-resolution genome-wide SNP and copy number survey that most if not all metastatic prostate cancers have monoclonal origins and maintain a unique signature copy number pattern of the parent cancer cell while also accumulating a variable number of separate subclonally sustained changes. We find no relationship between anatomic site of metastasis and genomic copy number change pattern. Taken together with past animal and cytogenetic studies of metastasis7, and recent single-locus genetic data in prostate and other metastatic cancers8-10, it appears that despite common genomic heterogeneity in primary cancers, most metastatic cancers arise from a single precursor cancer cell. Methodologically, this study establishes that genomic archeology of multiple anatomically separate metastatic cancers in individuals can be used to define the salient genomic features of a parent cancer clone of proven lethal metastatic phenotype.
Project description:In current study, we applied array-CGH analysis to detect somatic copy number aberrations across tumor genome to help separate multiple primary lung cancers from metastasis cancers.
Project description:The incidence of breast cancer has been rapidly increasing in East Asia. This is the first study of genome wide copy number of breast cancer in East Asia. We conducted this study to compare the genetic alterations between East and West.
Project description:Eukaryotic cells maintain multiple copies of the mitochondrial genome, which is essential for cellular metabolism. Accordingly, alterations in the mitochondrial DNA (mtDNA) copy number are associated with severe human diseases and ageing. However, the mechanisms through which cells regulate mtDNA copy number and the cellular consequences of altered copy number remain poorly understood. Here, using budding yeast as a model, we show that mtDNA copy number is determined by the amount of three limiting factors, Mip1, Abf2, and Rim1. By synthetically tuning the concentrations of only these three proteins, we can modulate mtDNA dosage inside the cell. This revealed that cells are surprisingly robust to mtDNA copy number alterations, with increased copy numbers even accelerating cell growth. Our findings suggest that this robustness is due to protein dosage compensation and independent regulation of mitochondrial morphology. Mechanistically, we identified a critical role of the retrograde signalling pathway for this adaptation. We show that signalling from mitochondria to the nucleus is upregulated in cells with higher mtDNA copy number, and disruption of this regulation diminishes their faster growth. Taken together, our work reveals regulatory principles that allow cells to adapt to mtDNA copy number alterations.