<unk> ncer occurs when a single progenitor cell accumulates mutations and other changes in the DNA, histones, and other biochemical compounds that make up the cell's genome. The cell genome controls the structure of the cell's biochemical components, the biochemical reactions that occur within the cell, and the biological interactions of that cell with other cells. Certain combinations of mutations in the given progenitor cell ultimately result in that cell (also<unk> lled a<unk> ncer stem cell) displaying a number of abnormal, malignant cellular properties that, when taken together, are considered characteristic of<unk> ncer, including: *the ability to continue to divide perpetually, producing an exponentially (or near-exponentially) increasing number of new malignant<unk> ncerous "daughter cells" (uncontrolled mitosis); *the ability to penetrate normal body surfaces and barriers, and to bore into or through nearby body structures and tissues (local invasiveness); *the ability to spread to other sites within the body (metastasize) by penetrating or entering into the lymphatic vessels (regional metastasis) and/or the blood vessels (distant metastasis). If this process of continuous growth, local invasion, and regional and distant metastasis is not halted via a combination of stimulation of immunological defenses and medical treatment interventions, the result is that the host suffers a continuously increasing burden of tumor cells throughout the body. Eventually, the tumor burden increasingly interferes with normal biochemical functions<unk> rried out by the host's organs, and death ultimately ensues.<unk>  is but one form of<unk> ncer—one composed of cells that have developed the cytological appearance, histological architecture, or molecular characteristics of epithelial cells. A progenitor<unk>  stem cell<unk> n be formed from any of a number of oncogenic combinations of mutations in a totipotent cell, a multipotent cell, or a mature differentiated cell. Invasion and metastasis The hallmark of a malignant tumor is its tendency to invade and infiltrate local and adjacent structures and, eventually, spread from the site of its origin to non-adjacent regional and distant sites in the body, a process<unk> lled metastasis. If unchecked, tumor growth and metastasis eventually creates a tumor burden so great that the host succumbs.<unk>  metastasizes through both the lymph nodes and the blood. Mutation Whole genome sequencing has established the mutation frequency for whole human genomes. The mutation frequency in the whole genome between generations for humans (parent to child) is about 70 new mutations per generation.<unk> s, however, have much higher mutation frequencies. The particular frequency depends on tissue type, whether a mis-match DNA repair deficiency is present, and exposure to DNA damaging agents such as components of tobacco smoke. Tuna and Amos have summarized the mutation frequencies per megabase (Mb) in some<unk> s, as shown in the table (along with the indicated frequencies of mutations per genome). + Mutation frequencies Cell type Mutation frequency Per megabase Per diploid genome Germline 0.023 70 Prostate<unk> ncer 0.9 5,400 Colorectal<unk>  ~5 ~30,000 Microsatellite stable (MSS) colon<unk> ncer 2.8 16,800 Microsatellite instable (MSI) colon<unk> ncer (mismatch repair deficient) 47 282,000 Hepatocellular<unk>  4.2 25,200 Breast<unk> ncer 1.18–1.66 7,080–9,960 Lung<unk> ncer 17.7 106,200 Small cell lung<unk> ncer 7.4 44,400 Non-small cell lung<unk> ncer (smokers) 10.5 63,000 Non-small cell lung<unk> ncer (never-smokers) 0.6 3,600 Lung adenocarcinoma (smokers) 9.8 58,500 Lung adenocarcinoma (never-smokers) 1.7 10,200<unk> use of mutations The likely major underlying<unk> use of mutations in<unk> s is DNA damage. For example, in the<unk> se of lung<unk> ncer, DNA damage is<unk> used by agents in exogenous genotoxic tobacco smoke (e.g. acrolein, formaldehyde, acrylonitrile, 1,3-butadiene, acetaldehyde, ethylene oxide and isoprene). Endogenous (metabolically-caused) DNA damage is also very frequent, occurring on average more than 60,000 times a day in the genomes of human cells. Externally and endogenously<unk> used damages may be converted into mutations by inaccurate translesion synthesis or inaccurate DNA repair (e.g. by non-homologous end joining). High frequency The high frequency of mutations in the total genome within<unk> s suggests that, often, an early<unk> rcinogenic alteration may be a deficiency in DNA repair. For instance, mutation rates substantially increase (sometimes by 100-fold) in cells defective in DNA mismatch repair A deficiency in DNA repair, itself,<unk> n allow DNA damages to accumulate, and error-prone translesion synthesis past some of those damages may give rise to mutations. In addition, faulty repair of these accumulated DNA damages may give rise to epigenetic alterations or epimutations. While a mutation or epimutation in a DNA repair gene, itself, would not confer a selective advantage, such a repair defect may be<unk> rried along as a passenger in a cell when the cell acquires an additional mutation/epimutation that does provide a proliferative advantage. Such cells, with both proliferative advantages and one or more DNA repair defects <unk> using a very high mutation rate), likely give rise to the high frequency of total genome mutations seen in<unk> s. DNA repair In somatic cells, deficiencies in DNA repair sometimes arise by mutations in DNA repair genes, but much more often are due to epigenetic reductions in expression of DNA repair genes. Thus, in a sequence of 113 colorectal<unk> s, only four had somatic missense mutations in the DNA repair gene MGMT, while the majority of these<unk> ncers had reduced MGMT protein expression due to methylation of the MGMT promoter region.
Carcinoma
Papilloma
Papillomatosis
Acinic cell carcinoma
Carcinosis
Condyloma
Colorectal adenoma
Calcinosis