Introduction
Term | Definition |
---|---|
5′UTR | The 5′ untranslated region is located downstream of where transcription begins but upstream of the first protein-coding region |
A:T-to-T:A transversions | The substitution of a purine for a pyrimidine or vice versa in DNA. This changes the base from adenine (A) to thymine (T) (or vice versa) |
Allele | Different versions of the same gene are called alleles. Humans have two alleles at each genetic locus, with one allele inherited from each parent |
Arm-level loss | Loss of genetic material from the end of a chromosome (telomere) to the centre (centromere) |
Autosome | Any chromosome that is not a sex chromosome (i.e., in chromosomes 1–22 in humans) |
Bi-allelic knockout | Inactivation of both copies of a gene |
Chromatin | Chromatin is a set of molecules found in cells whose primary function is to package DNA into a more compact structure |
Clonal expansion | In cancer evolution, clonal expansion is the production of daughter cells with the same genetic makeup as the original cell |
Convergent evolution | A process where independent clones evolve with similar traits, likely as a result of pressures to survive and grow within the tumour microenvironment |
Copy number aberration | Gain or loss of part of a chromosome |
Driver gene | A driver gene is one whose mutations increase the oncogenic potential of a tumour |
Epigenetic | Epigenetic refers to non-genetic influences on gene expression |
Epithelial to mesenchyme transition | Epithelial–mesenchymal transition describes the process by which epithelial cells lose their cell polarity and cell–cell adhesion, and gain migratory and invasive properties |
Focal deletions | Deletion of genomic material within a chromosome spanning in general less than 5 million base pairs |
Gene fusion | The result of a re-arrangement between different parts of the genome that aligns two genes |
Germline mutation | A germline mutation is one present in the germ cells, i.e., can be passed onto offspring |
GWAS | A genome-wide association study (GWAS), is an observational study of a genome-wide set of genetic variants in different individuals to see if any variant is associated with a trait |
Haploinsufficiency | Presence of only one functional copy of a gene (see mono-allelic inactivation) |
Loci | Loci refers to a position within the genome |
Loss of heterozygosity | The loss of one allele of a genetic locus |
Methyltransferase | Methyltransferases are a large group of enzymes that all methylate their substrates. In genetics, this affects gene transcription |
Mono-allelic inactivation | Inactivation of one copy of a gene. We are born with two copies of all genes (aside from those on the sex chromosomes) |
Mutational burden | The total number of mutations present within a cell or tumour |
Mutational signature | For the context of this paper, mutational signatures relate to the effect of mutational processes such as age or smoking on the specific types of point mutation seen in the tumour. For instance, signature 1 is found in all cancer types and is associated with age at diagnosis. Signature 2 is attributed to the AID/APOBEC family of cytidine deaminases. See https://cancer.sanger.ac.uk/cosmic/signatures for details |
Non-synonymous mutation | A mutation in the protein-coding part of the genome that results in a change in the resulting amino acid sequence |
Point mutations | Alteration of a single base in the genome to an alternative base |
Proto-oncogene | A normal gene which, when altered by mutation, becomes an oncogene—one that can contribute to cancer |
Somatic mutation | Mutations that are acquired during the lifetime of an individual, i.e., are not inherited |
Splice-site variants | A genetic alteration in the DNA sequence that occurs at the boundary of a protein-coding and non-coding region. This change can, therefore, alter the protein-coding sequence |
Stochastically | A random probability distribution that cannot be precisely predicted |
Structural variants | Variation in the structure of a chromosome. This encompasses many changes including the abnormal joining of different chromosomal regions and copy number aberrations |
Telomeres | Repetitive genetic sequence at the ends of a chromosome that protect against degradation or fusion with other chromosomes |
Trisomy | A trisomy is where there are three copies of a particular chromosome, instead of the normal two (in humans) |
Ubiquitination | The addition of ubiquitin to a substrate protein which affects their subsequent use, interaction, localisation, or breakdown |
Warburg-like metabolic shift | This is a phenomenon, whereby cells can produce additional energy through increased oxygen-dependent glycolysis followed by lactic acid fermentation |
Methods | Explanation |
---|---|
Cytogenetics | These are methods used to study the structure and function of chromosomes. In cancer, they commonly refer to methods such as karyotyping, fluorescent in situ hybridisation (FISH), and comparative genomic hybridization (CGH), and give an overview of which areas of the chromosome may have been lost or gained during oncogenesis |
Polymerase chain reaction (PCR) | The amplification of a few copies of a short region of DNA, generating thousands to millions of copies of this sequence. This allows the detection of mutations within the amplified sequence |
Next generation sequencing | Next generation sequencing (NGS), massively parallel or deep sequencing are related terms that describe a DNA sequencing technology that can sequence an entire human genome within a single day. This is a catch-all term used to describe a number of different sequencing technologies such as Illumina (Solexa), Roche 454, Ion torrent or SOLiD sequencing |
Methods
Results
Clear cell renal cell carcinoma
Epidemiology and genetics
Name | Chromosome band | Possible gene | Putative mechanism | References |
---|---|---|---|---|
rs11894252 | 2p21 |
EPAS1
| Transcription factor encoding hypoxia-inducible-factor-2 alpha | [10] |
rs7579899 | 2p21 |
EPAS1
| Transcription factor encoding hypoxia-inducible-factor-2 alpha | [10] |
rs7105934 | 11q13.3 | – | – | [10] |
rs718314 | 12p11.23 |
ITPR
| Possibly through obesity related effects | [11] |
rs1049380 | 12p11.23 |
ITPR
| Possibly through obesity related effects | [11] |
rs12105918 | 2q22.3 |
ZEB2
| Regulation of the epithelial to mesenchyme transition | [12] |
rs35252396 | 8q24.21 | – | Within potential regulatory region associated with other solid cancers | [13] |
rs4381241 | 1p32.3 |
FAF1
| Facilitates increased expression of genes driving cell proliferation | [14] |
rs67311347 | 3p22.1 |
CTNNB1
| Facilitates increased expression of genes driving cell proliferation | [14] |
rs10936602 | 3q26.2 | [14] | ||
rs2241261 | 8p21.3 |
GFRA2
| Activation of the RET tyrosine kinase receptor | [14] |
rs11813268 | 10q24 |
OBFC1
| Regulator of telomere length | [14] |
rs74911261 | 11q22.3 |
KDELC2
| Functional disruption in endoplasmic reticulum | [14] |
rs4903064 | 14q24.2 |
DPF3
| Chromatin remodelling | [14] |