Neoplasm

From Wikipedia, the free encyclopedia
  (Redirected from Neoplasia)
Jump to: navigation, search
Not to be confused with Pleonasm.
"Neoplastic" redirects here. For Dutch artistic movement, see De Stijl.
–plasia
Anaplasia cellular dedifferentiation
Aplasia organ or part of organ missing
Hypoplasia below-average (especially an inadequate) number of cells
Hyperplasia proliferation of cells
Neoplasia abnormal proliferation
Dysplasia change in cell or tissue phenotype
Metaplasia conversion in cell type
Prosoplasia development of new cell function
Desmoplasia connective tissue growth
Neoplasm
Classification and external resources
ICD-10 C00-D48
ICD-9 140-239.99
DiseasesDB 28841
MedlinePlus 001310.
MeSH D009369
Colectomy specimen containing a malignant neoplasm, namely an invasive colorectal carcinoma (the crater-like, reddish, irregularly shaped tumor)
Diagram illustrating benign neoplasms, namely fibroids of the uterus

Neoplasm (from ancient Greek νεο- neo-, "new" + πλάσμα plasma, "formation", "creation") is an abnormal mass of tissue as a result of neoplasia. Neoplasia is the abnormal growth or division of cells. Prior to neoplasia, cells often undergo an abnormal pattern of growth, such as metaplasia or dysplasia.[1] However, metaplasia or dysplasia do not always progress to neoplasia. The growth of neoplastic cells exceeds, and is not coordinated with, that of the normal tissues around it. The growth persists in the same excessive manner even after cessation of the stimuli. It usually causes a lump or tumor. Neoplasms may be benign, pre-malignant (carcinoma in situ) or malignant (cancer).

In modern medicine, the term tumor means a neoplasm that has formed a lump. In the past, the term tumor was used differently. Some neoplasms do not cause a lump.

Contents

Types [edit]

A neoplasm can be benign, potentially malignant (pre-cancer), or malignant (cancer).[2]

  • Benign neoplasms include uterine fibroids and melanocytic nevi (skin moles). They are circumscribed and localized and do not transform into cancer.[1]
  • Potentially malignant neoplasms include carcinoma in situ. They do not invade and destroy but, given enough time, will transform into a cancer.
  • Malignant neoplasms are commonly called cancer. They invade and destroy the surrounding tissue, may form metastases and eventually kill the host.
  • Secondary neoplasm refers to any of a class of cancerous tumor that is either a metastatic offshoot of a primary tumor, or an apparently unrelated tumor that increases in frequency following certain cancer treatments such as chemotherapy or radiotherapy.

Difficulty of definition [edit]

Because neoplasia includes very different diseases, it is difficult to find an all-encompassing definition.[3] The definition of the British oncologist R.A. Willis is widely cited: "A neoplasm is an abnormal mass of tissue, the growth of which exceeds and is uncoordinated with that of the normal tissues, and persists in the same excessive manner after cessation of the stimulus which evoked the change."[4] This definition is criticized because some neoplasms, such as nevi, are not progressive.

Clonality [edit]

Neoplastic tumors often contain more than one type of cell, but their initiation and continued growth is usually dependent on a single population of neoplastic cells. These cells are presumed to be clonal – that is, they are descended from a single progenitor cell.

Sometimes, the neoplastic cells all carry the same genetic or epigenetic anomaly that becomes evidence for clonality. For lymphoid neoplasms, e.g. lymphoma and leukemia, clonality is proven by the amplification of a single rearrangement of their immunoglobulin gene (for B cell lesions) or T-cell receptor gene (for T cell lesions). The demonstration of clonality is now considered to be necessary to identify a lymphoid cell proliferation as neoplastic.[5]

It is tempting to define neoplasms as clonal cellular proliferations but the demonstration of clonality is not always possible. Therefore, clonality is not required in the definition of neoplasia.

Neoplasia vs. tumor [edit]

Tumor (Latin for swelling, one of the cardinal signs of inflammation) originally meant any form of swelling, neoplastic or not. Current English, however, both medical and non-medical, uses tumor as a synonym of neoplasm.[6]

Some neoplasms do not form a tumor. These include leukemia and most forms of carcinoma in situ.

Malignant neoplasms [edit]

Primary causes: DNA damage/deficient DNA repair [edit]

The central role of DNA damage and epigenetic defects in DNA repair genes in malignant neoplasms

DNA damage is considered to be the primary underlying cause of malignant neoplasms (cancers).[7] Its central role in progression to cancer is illustrated in the figure in this section, in the box near the top. (The central features of DNA damage, epigenetic alterations and deficient DNA repair in progression to cancer are shown in red.) DNA damage is very common. Naturally occurring DNA damages (mostly due to cellular metabolism and the properties of DNA in water at body temperatures) occur at a rate of more than 10,000 new damages, on average, per human cell, per day [see article DNA damage (naturally occurring) ]. Additional DNA damages can arise from exposure to exogenous agents. Tobacco smoke causes increased exogenous DNA damage, and these DNA damages are the likely cause of lung cancer due to smoking.[8] UV light from solar radiation causes DNA damage that is important in melanoma.[9] Helicobacter pylori infection produces high levels of reactive oxygen species that damage DNA and contributes to gastric cancer.[10] Bile acids, at high levels in the colons of humans eating a high fat diet, also cause DNA damage and contribute to colon cancer.[11] Katsurano et al. indicated that macrophages and neutrophils in an inflamed colonic epithelium are the source of reactive oxygen species causing the DNA damages that initiate colonic tumorigenesis.[12] Some sources of DNA damage are indicated in the boxes at the top of the figure in this section.

Individuals with a germ line mutation causing deficiency in any of 34 DNA repair genes (see article DNA repair-deficiency disorder) are at increased risk of cancer. Some germ line mutations in DNA repair genes cause up to 100% lifetime chance of cancer (e.g. p53 mutations).[13] These germ line mutations are indicated in a box at the left of the figure with an arrow indicating their contribution to DNA repair deficiency.

About 70% of malignant neoplasms have no hereditary component and are called "sporadic cancers".[14] Only a minority of sporadic cancers have a deficiency in DNA repair due to mutation in a DNA repair gene. However, a majority of sporadic cancers have deficiency in DNA repair due to epigenetic alterations that reduce or silence DNA repair gene expression. For example, for 113 sequential colorectal cancers, only four had a missense mutation in the DNA repair gene MGMT, while the majority had reduced MGMT expression due to methylation of the MGMT promoter region (an epigenetic alteration).[15] Five reports present evidence that between 40% and 90% of colorectal cancers have reduced MGMT expression due to methylation of the MGMT promoter region.[16][17][18][19][20]

Similarly, out of 119 cases of mismatch repair-deficient colorectal cancers that lacked DNA repair gene PMS2 expression, PMS2 was deficient in 6 due to mutations in the PMS2 gene, while in 103 cases PMS2 expression was deficient because its pairing partner MLH1 was repressed due to promoter methylation (PMS2 protein is unstable in the absence of MLH1).[21] In the other 10 cases, loss of PMS2 expression was likely due to epigenetic overexpression of the microRNA, miR-155, which down-regulates MLH1.[22]

In further examples [tabulated in the article Epigenetics (see section “DNA repair epigenetics in cancer”)], epigenetic defects were found at frequencies of between 13%-100% for the DNA repair genes BRCA1, WRN, FANCB, FANCF, MGMT, MLH1, MSH2, MSH4, ERCC1, XPF, NEIL1 and ATM. These epigenetic defects occurred in various cancers (e.g. breast, ovarian, colorectal and head and neck). Two or three deficiencies in expression of ERCC1, XPF and/or PMS2 occur simultaneously in the majority of the 49 colon cancers evaluated by Facista et al.[23] Epigenetic alterations causing reduced expression of DNA repair genes is shown in a central box at the third level from the top of the figure in this section, and the consequent DNA repair deficiency is shown at the fourth level.

When expression of DNA repair genes is reduced, DNA damages accumulate in cells at a higher than normal level, and these excess damages cause increased frequencies of mutation and/or epimutation. Mutation rates strongly increase in cells defective in DNA mismatch repair[24][25] or in homologous recombinational repair (HRR).[26]

During repair of DNA double strand breaks, or repair of other DNA damages, incompletely cleared sites of repair can cause epigenetic gene silencing.[27][28] DNA repair deficiencies (level 4 in the figure) cause increased DNA damages (level 5 in the figure) which result in increased somatic mutations and epigenetic alterations (level 6 in the figure).

Field defects, normal appearing tissue with multiple alterations (and discussed in the section below), are common precursors to development of the disordered and improperly proliferating clone of tissue in a malignant neoplasm. Such field defects (second level from bottom of figure) may have multiple mutations and epigenetic alterations.

Once a cancer is formed, it usually has genome instability. This instability is likely due to reduced DNA repair or excessive DNA damage. Because of such instability, the cancer continues to evolve and to produce sub clones. For example, a renal cancer, sampled in 9 areas, had 40 ubiquitous mutations (i.e. present in all areas of the cancer), 59 mutations shared by some (but not all areas), and 29 “private” mutations only present in one of the areas of the cancer.[29]

Field defects in progression to cancer [edit]

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.

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.[30] 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.[31][32] However, in most cancer research, as pointed out by Rubin[33] “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…[34]” Similarly, Vogelstein et al.[35] 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.

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
Cancer Gene Frequency in Cancer Frequency in Field Defect Ref.
Colorectal MGMT 46% 34% 1
Colorectal MGMT 47% 11% 2
Colorectal MGMT 70% 60% 3
Colorectal MSH2 13% 5% 2
Colorectal ERCC1 100% 40% 4
Colorectal PMS2 88% 50% 4
Colorectal XPF 55% 40% 4
Head and Neck MGMT 54% 38% 5
Head and Neck MLH1 33% 25% 6
Head and Neck MLH1 31% 20% 7
Stomach MGMT 88% 78% 8
Stomach MLH1 73% 20% 9
Esophagus MLH1 77%-100% 23%-79% 10

References in the table are given here: 1,[36] 2,[18] 3,[37] 4,[23] 5,[38] 6,[39] 7,[40] 8,[41] 9,[42] 10,[43]

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.[44]

Genome instability in cancer [edit]

Cancers are known to exhibit genome instability or a mutator phenotype.[45] The protein-coding DNA within the nucleus is about 1.5% of the total genomic DNA.[46] 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[35] 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.[47] In an average melanoma tissue sample (where melanomas have a higher exome mutation frequency[35]) the total number of DNA sequence mutations is about 80,000.[48] These 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.[23] to frequently have epigenetic defects in 2 or 3 DNA repair proteins (ERCC1, XPF and/or PMS2) in the entire area of the field defect. Deficiencies in DNA repair cause increased mutation rates.[24][25][26] 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 and/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 cell acquires an additional mutation/epimutation that does provide a proliferative advantage.

See also [edit]

References [edit]

  1. ^ a b Abrams, Gerald. "Neoplasia I". Retrieved 23 January 2012. 
  2. ^ "Cancer - Activity 1 - Glossary, page 4 of 5". Retrieved 2008-01-08. 
  3. ^ "What is neoplasm? Find the definition for neoplasm at WebMD". Retrieved 2008-01-08. 
  4. ^ Willis RA. The Spread of Tumors in the Human Body. London, Butterworth & Co, 1952
  5. ^ Lee ES, Locker J, Nalesnik M, et al. (1995). "The association of Epstein-Barr virus with smooth-muscle tumors occurring after organ transplantation". N. Engl. J. Med. 332 (1): 19–25. doi:10.1056/NEJM199501053320104. PMID 7990861. 
  6. ^ "Pancreas Cancer: Glossary of Terms". Retrieved 2008-01-08. 
  7. ^ Bernstein C. (2009). DNA Damage and Cancer. Sciverse Elsevier Publishers http://www.scitopics.com/DNA_Damage_and_Cancer.html
  8. ^ Cunningham FH, Fiebelkorn S, Johnson M, Meredith C. (2011). A novel application of the Margin of Exposure approach: segregation of tobacco smoke toxicants. Food Chem Toxicol 49(11) 2921-2933. PMID 21802474
  9. ^ Kanavy HE, Gerstenblith MR. (2011). Ultraviolet radiation and melanoma. Semin Cutan Med Surg 30(4) 222-228. PMID 22123420
  10. ^ Handa O, Naito Y, Yoshikawa T. (2011). Redox biology and gastric carcinogenesis: the role of Helicobacter pylori. Redox Rep 16(1) 1-7. PMID 21605492
  11. ^ Bernstein C, Holubec H, Bhattacharyya AK, Nguyen H, Payne CM, Zaitlin B, Bernstein H. (2011). Carcinogenicity of deoxycholate, a secondary bile acid. Arch Toxicol 85(8):863-71. doi: 10.1007/s00204-011-0648-7. PMID 21267546 http://www.ncbi.nlm.nih.gov/pubmed/?term=Bernstein+C%2C+Holubec+H%2C+Bhattacharyya+AK%2C+Nguyen+H
  12. ^ Katsurano M, Niwa T, Yasui Y, Shigematsu Y, Yamashita S, Takeshima H, Lee MS, Kim YJ, Tanaka T, Ushijima T. Early-stage formation of an epigenetic field defect in a mouse colitis model, and non-essential roles of T- and B-cells in DNA methylation induction. Oncogene 2012; 31: 342-351 PMID 21685942 DOI: 10.1038/onc.2011.241
  13. ^ Malkin D. (2011). Li-fraumeni syndrome. Genes Cancer 2(4) 475-484. PMID 21779515
  14. ^ Lichtenstein P, Holm NV, Verkasalo PK, Iliadou A, Kaprio J, Koskenvuo M, Pukkala E, Skytthe A, Hemminki K. Environmental and heritable factors in the causation of cancer--analyses of cohorts of twins from Sweden, Denmark, and Finland. N Engl J Med 2000;343(2) 78-85. PMID 10891514
  15. ^ Halford S, Rowan A, Sawyer E, Talbot I, Tomlinson I. (2005). O(6)-methylguanine methyltransferase in colorectal cancers: detection of mutations, loss of expression, and weak association with G:C>A:T transitions. Gut 54(6):797-802. PMID 15888787 http://www.ncbi.nlm.nih.gov/pubmed/15888787
  16. ^ Shen L, Kondo Y, Rosner GL, Xiao L, Hernandez NS, Vilaythong J, Houlihan PS, Krouse RS, Prasad AR, Einspahr JG, Buckmeier J, Alberts DS, Hamilton SR, Issa JP (2005). MGMT promoter methylation and field defect in sporadic colorectal cancer. J Natl Cancer Inst 97(18) 1330-1338. PMID 16174854
  17. ^ Psofaki V, Kalogera C, Tzambouras N, Stephanou D, Tsianos E, Seferiadis K, Kolios G (2010). Promoter methylation status of hMLH1, MGMT, and CDKN2A/p16 in colorectal adenomas. World J Gastroenterol 16(28) 3553-3560. PMID 20653064 PMCID: PMC2909555
  18. ^ a b Lee KH, Lee JS, Nam JH, Choi C, Lee MC, Park CS, Juhng SW, Lee JH (2011). Promoter methylation status of hMLH1, hMSH2, and MGMT genes in colorectal cancer associated with adenoma-carcinoma sequence. Langenbecks Arch Surg 396(7) 1017-1026. PMID 21706233
  19. ^ Amatu A, Sartore-Bianchi A, Moutinho C, Belotti A, Bencardino K, Chirico G, Cassingena A, Rusconi F, Esposito A, Nichelatti M, Esteller M, Siena S (2013). Promoter CpG Island Hypermethylation of the DNA Repair Enzyme MGMT Predicts Clinical Response to Dacarbazine in a Phase II Study for Metastatic Colorectal Cancer. Clin Cancer Res [Epub ahead of print] PMID 23422094
  20. ^ Mokarram P, Zamani M, Kavousipour S, Naghibalhossaini F, Irajie C, Moradi Sarabi M, Hosseini SV (2012). Different patterns of DNA methylation of the two distinct O6-methylguanine-DNA methyltransferase (O(6)-MGMT) promoter regions in colorectal cancer. Mol Biol Rep Dec 28. [Epub ahead of print] PMID 23271133
  21. ^ Truninger K, Menigatti M, Luz J, Russell A, Haider R, Gebbers JO, Bannwart F, Yurtsever H, Neuweiler J, Riehle HM, Cattaruzza MS, Heinimann K, Schär P, Jiricny J, Marra G. (2005). Immunohistochemical analysis reveals high frequency of PMS2 defects in colorectal cancer. Gastroenterology 128:1160-1171. PMID 15887099
  22. ^ Valeri N, Gasparini P, Fabbri M, Braconi C, Veronese A, Lovat F, Adair B, Vannini I, Fanini F, Bottoni A, Costinean S, Sandhu SK, Nuovo GJ, Alder H, Gafa R, Calore F, Ferracin M, Lanza G, Volinia S, Negrini M, Mcllhatton MA, Amadori D, Fishel R, Croce CM: Modulation of mismatch repair and genomic stability by miR-155. Proc Natl Acad Sci USA 2010, 107:6982-6987. PMID 20351277
  23. ^ a b c Facista A, Nguyen H, Lewis C, Prasad AR, Ramsey L, Zaitlin B, Nfonsam V, Krouse RS, Bernstein H, Payne CM, Stern S, Oatman N, Banerjee B, Bernstein C. (2012). Deficient expression of DNA repair enzymes in early progression to sporadic colon cancer. Genome Integr. 3(1):3. doi: 10.1186/2041-9414-3-3. PMID 22494821 http://www.ncbi.nlm.nih.gov/pubmed/22494821
  24. ^ a b Narayanan L, Fritzell JA, Baker SM, Liskay RM, Glazer PM. (1997). Elevated levels of mutation in multiple tissues of mice deficient in the DNA mismatch repair gene Pms2. Proc Natl Acad Sci U S A 94(7) 3122-3127. PMID 9096356
  25. ^ a b Hegan DC, Narayanan L, Jirik FR, Edelmann W, Liskay RM, Glazer PM. (2006). Differing patterns of genetic instability in mice deficient in the mismatch repair genes Pms2, Mlh1, Msh2, Msh3 and Msh6. Carcinogenesis 27(12) 2402-2408. PMID 16728433
  26. ^ a b Tutt AN, van Oostrom CT, Ross GM, van Steeg H, Ashworth A. (2002). Disruption of Brca2 increases the spontaneous mutation rate in vivo: synergism with ionizing radiation. EMBO Rep 3(3) 255-260. PMID 11850397
  27. ^ O'Hagan HM, Mohammad HP, Baylin SB. (2008) Double strand breaks can initiate gene silencing and SIRT1-dependent onset of DNA methylation in an exogenous promoter CpG island. PLoS Genet. 4(8):e1000155. PMID 18704159
  28. ^ Cuozzo C, Porcellini A, Angrisano T, Morano A, Lee B, Di Pardo A, Messina S, Iuliano R, Fusco A, Santillo MR, Muller MT, Chiariotti L, Gottesman ME, Avvedimento EV (2007). DNA damage, homology-directed repair, and DNA methylation. PLoS Genet 3(7):e110. PMID 17616978
  29. ^ Gerlinger M, Rowan AJ, Horswell S, Larkin J, Endesfelder D, Gronroos E, Martinez P, Matthews N, Stewart A, Tarpey P, Varela I, Phillimore B, Begum S, McDonald NQ, Butler A, Jones D, Raine K, Latimer C, Santos CR, Nohadani M, Eklund AC, Spencer-Dene B, Clark G, Pickering L, Stamp G, Gore M, Szallasi Z, Downward J, Futreal PA, Swanton C. (2012). Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N Engl J Med 366(10) 883-892. PMID 22397650
  30. ^ Slaughter DP, Southwick HW, Smejkal W. (1953). Field cancerization in oral stratified squamous epithelium; clinical implications of multicentric origin. Cancer 6: 963-968. PMID 13094644
  31. ^ Bernstein C, Bernstein H, Payne CM, Dvorak K, Garewal H. (2008). Field defects in progression to gastrointestinal tract cancers. Cancer Lett 260(1-2):1-10. doi: 10.1016/j.canlet.2007.11.027. Review. PMID 18164807 http://www.ncbi.nlm.nih.gov/pubmed/18164807
  32. ^ Nguyen H, Loustaunau C, Facista A, Ramsey L, Hassounah N, Taylor H, Krouse R, Payne CM, Tsikitis VL, Goldschmid S, Banerjee B, Perini RF, Bernstein C. (2010). Deficient Pms2, ERCC1, Ku86, CcOI in field defects during progression to colon cancer. J Vis Exp (41). doi:pii: 1931. 10.3791/1931. PMID 20689513 The 28 minute video in this article is best watched by clicking on “Download video file” under the image in the abstract at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3149991/
  33. ^ Rubin H. (2011). Fields and field cancerization: the preneoplastic origins of cancer: asymptomatic hyperplastic fields are precursors of neoplasia, and their progression to tumors can be tracked by saturation density in culture. Bioessays 33: 224-231 PMID 21254148 DOI: 10.1002/bies.201000067
  34. ^ Tsao JL, Yatabe Y, Salovaara R, Järvinen HJ, Mecklin JP, Aaltonen LA, Tavaré S, Shibata D. (2000). Genetic reconstruction of individual colorectal tumor histories. Proc Natl Acad Sci U S A 97: 1236-1241 PMID 10655514.
  35. ^ a b c Vogelstein B, Papadopoulos N, Velculescu VE, Zhou S, Diaz LA Jr, Kinzler KW. (2013). Cancer genome landscapes. Science 339(6127):1546-58. doi: 10.1126/science.1235122. Review. PMID 23539594
  36. ^ Shen L, Kondo Y, Rosner GL, Xiao L, Hernandez NS, Vilaythong J, Houlihan PS, Krouse RS, Prasad AR, Einspahr JG, Buckmeier J, Alberts DS, Hamilton SR, Issa JP. (2005). MGMT promoter methylation and field defect in sporadic colorectal cancer. J Natl Cancer Inst 97(18) 1330-1338. PMID 16174854
  37. ^ Svrcek M, Buhard O, Colas C, Coulet F, Dumont S, Massaoudi I, Lamri A, Hamelin R, Cosnes J, Oliveira C, Seruca R, Gaub MP, Legrain M, Collura A, Lascols O, Tiret E, Fléjou JF, Duval A. (2010). Methylation tolerance due to an O6-methylguanine DNA methyltransferase (MGMT) field defect in the colonic mucosa: an initiating step in the development of mismatch repair-deficient colorectal cancers. Gut 59(11):1516-26. doi: 10.1136/gut.2009.194787. PMID 20947886
  38. ^ Paluszczak J, Misiak P, Wierzbicka M, Woźniak A, Baer-Dubowska W. (2011). Frequent hypermethylation of DAPK, RARbeta, MGMT, RASSF1A and FHIT in laryngeal squamous cell carcinomas and adjacent normal mucosa. Oral Oncol 47(2):104-7. doi: 10.1016/j.oraloncology.2010.11.006. PMID 21147548
  39. ^ Zuo C, Zhang H, Spencer HJ, Vural E, Suen JY, Schichman SA, Smoller BR, Kokoska MS, Fan CY. (2009). Increased microsatellite instability and epigenetic inactivation of the hMLH1 gene in head and neck squamous cell carcinoma. Zuo C, Zhang H, Spencer HJ, Vural E, Suen JY, Schichman SA, Smoller BR, Kokoska MS, Fan CY. Otolaryngol Head Neck Surg 141(4):484-90. doi: 10.1016/j.otohns.2009.07.007. PMID 19786217
  40. ^ Tawfik HM, El-Maqsoud NM, Hak BH, El-Sherbiny YM. (2011). Head and neck squamous cell carcinoma: mismatch repair immunohistochemistry and promoter hypermethylation of hMLH1 gene. Am J Otolaryngol 32(6):528-36. doi: 10.1016/j.amjoto.2010.11.005. PMID 21353335
  41. ^ Zou XP, Zhang B, Zhang XQ, Chen M, Cao J, Liu WJ. (2009). Promoter hypermethylation of multiple genes in early gastric adenocarcinoma and precancerous lesions. Hum Pathol 40(11):1534-42. doi: 10.1016/j.humpath.2009.01.029. PMID 19695681
  42. ^ Wani M, Afroze D, Makhdoomi M, Hamid I, Wani B, Bhat G, Wani R, Wani K. (2012). Promoter methylation status of DNA repair gene (hMLH1) in gastric carcinoma patients of the Kashmir valley. Asian Pac J Cancer Prev 13(8):4177-4181. PMID 23098428
  43. ^ Agarwal A, Polineni R, Hussein Z, Vigoda I, Bhagat TD, Bhattacharyya S, Maitra A, Verma A. (2012). Role of epigenetic alterations in the pathogenesis of Barrett's esophagus and esophageal adenocarcinoma. Int J Clin Exp Pathol 5(5):382-96. Review. PMID 22808291
  44. ^ Hofstad B, Vatn MH, Andersen SN, Huitfeldt HS, Rognum T, Larsen S, Osnes M. (1996). Growth of colorectal polyps: redetection and evaluation of unresected polyps for a period of three years. Gut 39(3):449-456. PMID 8949653
  45. ^ Schmitt MW, Prindle MJ, Loeb LA. (2012). Implications of genetic heterogeneity in cancer. Ann N Y Acad Sci. 2012 Sep;1267:110-6. doi: 10.1111/j.1749-6632.2012.06590.x. PMID 22954224
  46. ^ International Human Genome Sequencing Consortium (2001). "Initial sequencing and analysis of the human genome". Nature 409 (6822): 860–921. doi:10.1038/35057062. PMID 11237011.
  47. ^ Yost SE, Smith EN, Schwab RB, Bao L, Jung H, Wang X, Voest E, Pierce JP, Messer K, Parker BA, Harismendy O, Frazer KA. (2012). Identification of high-confidence somatic mutations in whole genome sequence of formalin-fixed breast cancer specimens. Nucleic Acids Res 40(14):e107. PMID 22492626
  48. ^ Berger MF, Hodis E, Heffernan TP, Deribe YL, Lawrence MS, Protopopov A, Ivanova E, Watson IR, Nickerson E, Ghosh P, Zhang H, Zeid R, Ren X, Cibulskis K, Sivachenko AY, Wagle N, Sucker A, Sougnez C, Onofrio R, Ambrogio L, Auclair D, Fennell T, Carter SL, Drier Y, Stojanov P, Singer MA, Voet D, Jing R, Saksena G, Barretina J, Ramos AH, Pugh TJ, Stransky N, Parkin M, Winckler W, Mahan S, Ardlie K, Baldwin J, Wargo J, Schadendorf D, Meyerson M, Gabriel SB, Golub TR, Wagner SN, Lander ES, Getz G, Chin L, Garraway LA. (2012). Melanoma genome sequencing reveals frequent PREX2 mutations. Nature 485(7399):502-6. doi: 10.1038/nature11071. PMID 22622578
Principles of pathology
Anatomical pathology
Clinical pathology
Specific conditions
Conditions
Benign tumors
Malignant progression
Topography
Histology
Other
Staging/grading
Carcinogenesis
Misc.
Carcinogen—Cancer causing materials and agents
Main articles
Major suspected carcinogens
IARC
See also
Neoplasm
Oncology
Retrieved from "http://en.wikipedia.org/w/index.php?title=Neoplasm&oldid=555278386"