59 mutations shared by some (but not all areas), and 29 "private" mutations only present in one of the areas of the cancer. field defects longitudinally opened freshly resected colon segment showing a cancer and four polyps, plus a schematic diagram indicating a likely field defect (a region of tissue that precedes and predisposes to the development of cancer) in this colon segment. the diagram indicates sub-clones and sub-sub-clones that were precursors to the tumors. various other terms have been used to describe this phenomenon, including "field effect", "field cancerization", and "field carcinogenesis". the term "field cancerization" was first used in 1953 to describe an area or "field" of epithelium that has been preconditioned by (at that time) largely unknown processes so as to predispose it towards development of cancer. since then, the terms "field cancerization" and "field defect" have been used to describe pre-malignant tissue in which new cancers are likely to arise. field defects are important in progression to cancer. however, in most cancer research, as pointed out by rubin "the vast majority of studies in cancer research has been done on well-defined tumors in vivo, or on discrete neoplastic foci in vitro. yet there is evidence that more than 80% of the somatic mutations found in mutator phenotype human colorectal tumors occur before the onset of terminal clonal expansion. similarly, vogelstein et al. point out that more than half of somatic mutations identified in tumors occurred in a pre-neoplastic phase (in a field defect), during growth of apparently normal cells. likewise, epigenetic alterations present in tumors may have occurred in pre-neoplastic field defects. an expanded view of field effect has been termed "etiologic field effect", which encompasses not only molecular and pathologic changes in pre-neoplastic cells but also influences of exogenous environmental factors and molecular changes in the local microenvironment on neoplastic evolution from tumor initiation to patient death. in the colon, a field defect probably arises by natural selection of a mutant or epigenetically altered cell among the stem cells at the base of one of the intestinal crypts on the inside surface of the colon. a mutant or epigenetically altered stem cell may replace the other nearby stem cells by natural selection. thus, a patch of abnormal tissue may arise. the figure in this section includes a photo of a freshly resected and lengthwise-opened segment of the colon showing a colon cancer and four polyps. below the photo, there is a schematic diagram of how a large patch of mutant or epigenetically altered cells may have formed, shown by the large area in yellow in the diagram. within this first large patch in the diagram (a large clone of cells), a second such mutation or epigenetic alteration may occur so that a given stem cell acquires an advantage compared to other stem cells within the patch, and this altered stem cell may expand clonally forming a secondary patch, or sub-clone, within the original patch. this is indicated in the diagram by four smaller patches of different colors within the large yellow original area. within these new patches (sub-clones), the process may be repeated multiple times, indicated by the still smaller patches within the four secondary patches (with still different colors in the diagram) which clonally expand, until stem cells arise that generate either small polyps or else a malignant neoplasm (cancer). in the photo, an apparent field defect in this segment of a colon has generated four polyps (labeled with the size of the polyps, 6mm, 5mm, and two of 3mm, and a cancer about 3 cm across in its longest dimension). these neoplasms are also indicated, in the diagram below the photo, by 4 small tan circles (polyps) and a larger red area (cancer). the cancer in the photo occurred in the cecal area of the colon, where the colon joins the small intestine (labeled) and where the appendix occurs (labeled). the fat in the photo is external to the outer wall of the colon. in the segment of colon shown here, the colon was cut open lengthwise to expose the inner surface of the colon and to display the cancer and polyps occurring within the inner epithelial lining of the colon. if the general process by which sporadic colon cancers arise is the formation of a pre-neoplastic clone that spreads by natural selection, followed by formation of internal sub-clones within the initial clone, and sub-sub-clones inside those, then colon cancers generally should be associated with, and be preceded by, fields of increasing abnormality reflecting the succession of premalignant events. the most extensive region of abnormality (the outermost yellow irregular area in the diagram) would reflect the earliest event in formation of a malignant neoplasm. in experimental evaluation of specific dna repair deficiencies in cancers, many specific dna repair deficiencies were also shown to occur in the field defects surrounding those cancers. the table, below, gives examples for which the dna repair deficiency in a cancer was shown to be caused by an epigenetic alteration, and the somewhat lower frequencies with which the same epigenetically caused dna repair deficiency was found in the surrounding field defect. frequency of epigenetic changes in dna repair genes in sporadic cancers and in adjacent field defects cancergenefrequency in cancerfrequency in field defectref. colorectal mgmt46%34% colorectal mgmt47%11% colorectal mgmt70%60% colorectal msh213%5% colorectal ercc1100%40% colorectal pms288%50% colorectal xpf55%40% head and neck mgmt54%38% head and neck mlh133%25% head and neck mlh131%20% stomach mgmt88%78% stomach mlh173%20% esophagus mlh177%-100%23%-79% some of the small polyps in the field defect shown in the photo of the opened colon segment may be relatively benign neoplasms. of polyps less than 10mm in size, found during colonoscopy and followed with repeat colonoscopies for 3 years, 25% were unchanged in size, 35% regressed or shrank in size while 40% grew in size. genome instability cancers are known to exhibit genome instability or a mutator phenotype. the protein-coding dna within the nucleus is about 1.5% of the total genomic dna. within this protein-coding dna (called the exome), an average cancer of the breast or colon can have about 60 to 70 protein altering mutations, of which about 3 or 4 may be "driver" mutations, and the remaining ones may be "passenger" mutations. however, the average number of dna sequence mutations in the entire genome (including non-protein-coding regions) within a breast cancer tissue sample is about 20,000. in an average melanoma tissue sample (where melanomas have a higher exome mutation frequency) the total number of dna sequence mutations is about 80,000. this compares to the very low mutation frequency of about 70 new mutations in the entire genome between generations (parent to child) in humans. the high frequencies of mutations in the total nucleotide sequences within cancers suggest that often an early alteration in the field defects giving rise to a cancer (e.g. yellow area in the diagram in this section) is a deficiency in dna repair. the large field defects surrounding colon cancers (extending to at about 10 cm on each side of a cancer) were shown by facista et al. to frequently have epigenetic defects in 2 or 3 dna repair proteins (ercc1, xpf or pms2) in the entire area of the field defect. deficiencies in dna repair cause increased mutation rates. a deficiency in dna repair, itself, can 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 epimutations. these new mutations or epimutations may provide a proliferative advantage, generating a field defect. although the mutations/epimutations in dna repair genes do not, themselves, confer a selective advantage, they may be carried along as passengers in cells when the cells acquire additional mutations/epimutations that do provide a proliferative advantage. etymology the term neoplasm is a synonym of tumor. neoplasia denotes the process of the formation of neoplasms/tumors, and the process is referred to as a neoplastic process. the word neoplastic itself comes from greek neo 'new' and plastic 'formed, molded'. the term tumor derives from the latin noun tumor 'a swelling', ultimately from the verb tumēre 'to swell'. in the british commonwealth, the spelling tumour is commonly used, whereas in the u.s. the word is usually spelled tumor. in its medical sense, tumor has traditionally meant an abnormal swelling of the flesh. the roman medical encyclopedist celsus (c. 30 bc–38 ad) described the four cardinal signs of acute inflammation as tumor, dolor, calor, and rubor (swelling, pain, increased heat, and redness). (his treatise, de medicina, was the first medical book printed in 1478 following the invention of the movable-type printing press.) in contemporary english, the word tumor is often used as a synonym for a cystic (liquid-filled) growth or solid neoplasm (cancerous or non-cancerous), with other forms of swelling often referred to as "swellings". related terms occur commonly in the medical literature, where the nouns tumefaction and tumescence (derived from the adjective tumescent) are current medical terms for non-neoplastic swelling. this type of swelling is most often caused by inflammation caused by trauma, infection, and other factors. tumors may be caused by conditions other than an overgrowth of neoplastic cells, however. cysts (such as sebaceous cysts) are also referred to as tumors, even though they have no neoplastic cells. this is standard in medical-billing terminology (especially when billing for a growth whose pathology has yet to be determined).