Editing Comparative genomic hybridization (section)

==Applications==

===Conventional===

Conventional CGH has been used mainly for the identification of chromosomal regions that are recurrently lost or gained in tumors, as well as for the diagnosis and prognosis of cancer.<ref>Weiss MM, Kuipers EJ, Meuwissen SG, van Diest PJ, Meijer GA (2003) Comparative genomic hybridization as a supportive tool in diagnostic pathology. J Clin Pathol 56:522–527.</ref> This approach can also be used to study [[chromosomal aberrations]] in [[fetal]] and [[neonatal]] genomes. Furthermore, conventional CGH can be used in detecting chromosomal abnormalities and have been shown to be efficient in diagnosing complex abnormalities associated with human genetic disorders.<ref name="Oostlander,Meijer,Ylstra" />

====In cancer research====
CGH data from several studies of the same tumor type show consistent patterns of non-random genetic aberrations.<ref name="Forozan,Karhu,Kononen,Kallioniemi,Kallioniemi">{{cite journal | vauthors = Forozan F, Karhu R, Kononen J, Kallioniemi A, Kallioniemi OP | year = 1997 | title = Genome screening by comparative genomic hybridization | journal = Trends Genet | volume = 13 | issue = 10| pages = 405–409 | doi=10.1016/s0168-9525(97)01244-4| pmid = 9351342 }}</ref> Some of these changes appear to be common to various kinds of malignant tumors, while others are more tumor specific. For example, gains of chromosomal regions lq, 3q and 8q, as well as losses of 8p, 13q, 16q and 17p, are common to a number of tumor types, such as breast, ovarian, prostate, renal and bladder cancer (Figure. 3). Other alterations, such as 12p and Xp gains in testicular cancer, 13q gain 9q loss in bladder cancer, 14q loss in renal cancer and Xp loss in ovarian cancer are more specific, and might reflect the unique selection forces operating during cancer development in different organs.<ref name="Forozan,Karhu,Kononen,Kallioniemi,Kallioniemi" /> Array CGH is also frequently used in research and diagnostics of B cell malignancies, such as chronic lymphocytic leukemia.

====Chromosomal aberrations====
[[Cri du Chat]] (CdC) is a syndrome caused by a partial deletion of the short arm of chromosome 5.<ref name="Levy,Dunn,Kern,Hirschhorn,Kardon">{{cite journal | vauthors = Levy B, Dunn TM, Kern JH, Hirschhorn K, Kardon NB | year = 2002 | title = Delineation of the dup5q phenotype by molecular cytogenetic analysis in a patient with dup5q/del 5p (Cri du Chat) | journal = Am J Med Genet | volume = 108 | issue = 3| pages = 192–197 | doi=10.1002/ajmg.10261| pmid = 11891684 }}</ref> Several studies have shown that conventional CGH is suitable to detect the deletion, as well as more complex chromosomal alterations. For example, Levy et al. (2002) reported an infant with a cat-like cry, the hallmark of CdC, but having an indistinct karyotype. CGH analysis revealed a loss of chromosomal material from 5p15.3 confirming the diagnosis clinically. These results demonstrate that conventional CGH is a reliable technique in detecting structural aberrations and, in specific cases, may be more efficient in diagnosing complex abnormalities.<ref name="Levy,Dunn,Kern,Hirschhorn,Kardon" />

===Array CGH===
Array CGH applications are mainly directed at detecting genomic abnormalities in cancer. However, array CGH is also suitable for the analysis of DNA copy number aberrations that cause human genetic disorders.<ref name="Oostlander,Meijer,Ylstra" /> That is, array CGH is employed to uncover deletions, amplifications, breakpoints and ploidy abnormalities. Earlier diagnosis is of benefit to the patient as they may undergo appropriate treatments and counseling to improve their prognosis.<ref name="Marquis-Nicholson,Aftimos,Hayes,George,Love" />

====Genomic abnormalities in cancer====
Genetic alterations and rearrangements occur frequently in cancer and contribute to its pathogenesis. Detecting these aberrations by array CGH provides information on the locations of important cancer genes and can have clinical use in diagnosis, cancer classification and prognostification.<ref name="Bejjani,Shaffer" /> However, not all of the losses of genetic material are pathogenetic, since some DNA material is physiologically lost during the rearrangement of immunoglobulin subgenes. In a recent study, array CGH has been implemented to identify regions of chromosomal aberration ([[copy-number variation]]) in several mouse models of breast cancer, leading to identification of cooperating genes during myc-induced oncogenesis.<ref name="aprelikova">{{cite journal | vauthors = Aprelikova O, Chen K, El Touny LH, Brignatz-Guittard C, Han J, Qiu T, Yang HH, Lee MP, Zhu M, Green JE | title = The epigenetic modifier JMJD6 is amplified in mammary tumors and cooperates with c-Myc to enhance cellular transformation, tumor progression, and metastasis | journal = Clin Epigenetics | volume = 8 | issue = 38 | pages = 38 | date = Apr 2016 | doi = 10.1186/s13148-016-0205-6 | pmid = 27081402 | pmc = 4831179 | doi-access = free }}</ref>

Array CGH may also be applied not only to the discovery of chromosomal abnormalities in cancer, but also to the monitoring of the progression of tumors. Differentiation between [[metastatic]] and mild lesions is also possible using FISH once the abnormalities have been identified by array CGH.<ref name="deRavel,Devriendt,Fryns,Vermeesch" /><ref name="Marquis-Nicholson,Aftimos,Hayes,George,Love" />

====Submicroscopic aberrations====
[[Prader–Willi syndrome]] (PWS) is a paternal structural abnormality involving 15q11-13, while a maternal aberration in the same region causes Angelman syndrome (AS). In both syndromes, the majority of cases (75%) are the result of a 3–5 Mb deletion of the PWS/AS critical region.<ref>L'Hermine AC, Aboura A, Brisset S, Cuisset L, Castaigne V, Labrune P, Frydman R, Tachdjian G. (2003) Fetal phenotype of Prader–Willi syndrome due to maternal disomy for chromosome 15. Prenat Diagn 23:938–943.</ref> These small aberrations cannot be detected using [[cytogenetics]] or conventional CGH, but can be readily detected using array CGH. As a proof of principle Vissers et al. (2003) constructed a genome wide array with a 1 Mb resolution to screen three patients with known, FISH-confirmed microdeletion syndromes, including one with PWS. In all three cases, the abnormalities, ranging from 1.5 to 2.9Mb, were readily identified.<ref>{{cite journal | vauthors = Vissers LE, de Vries BB, Osoegawa K, Janssen IM, Feuth T, Choy CO, Straatman H, van der Vliet W, Huys EH, van Rijk A, Smeets D, van Ravenswaaij-Arts CM, Knoers NV, van der Burgt I, de Jong PJ, Brunner HG, Geurts , van Kessel A, Schoenmakers EF, Veltman JA | year = 2003 | title = Array-based comparative genomic hybridization for the genome-wide detection of submicroscopic chromosomal abnormalities | journal = Am J Hum Genet | volume = 73 | issue = 6| pages = 1261–1270 | doi = 10.1086/379977 | pmid = 14628292 | pmc = 1180392 }}</ref> Thus, array CGH was demonstrated to be a specific and sensitive approach in detecting submicroscopic aberrations.

When using overlapping microarrays, it is also possible to uncover breakpoints involved in chromosomal aberrations.

====Prenatal genetic diagnosis====
Though not yet a widely employed technique, the use of array CGH as a tool for preimplantation genetic screening is becoming an increasingly popular concept. It has the potential to detect CNVs and [[aneuploidy]] in eggs, sperm or embryos which may contribute to failure of the embryo to successfully implant, miscarriage or conditions such as Down syndrome (trisomy 21). This makes array CGH a promising tool to reduce the incidence of life altering conditions and improve success rates of [[IVF]] attempts. The technique involves whole genome amplification from a single cell which is then used in the array CGH method. It may also be used in couples carrying [[chromosome translocations|chromosomal translocations]] such as balanced reciprocal translocations or Robertsonian translocations, which have the potential to cause chromosomal imbalances in their offspring.<ref name="Evangelidou,Alexandrou,Moutafi,Ioannides,Antonios,Koumbaris,Kallikas,Velissariou,Sismani,Patsalis" /><ref>{{cite journal | vauthors = Fiorentino F | s2cid = 6484211 | year = 2012 | title = Array comparative genomic hybridization: its role in preimplantation genetic diagnosis | journal = Current Opinion in Obstetrics and Gynecology | volume = 24 | issue = 4| pages = 203–209 | doi=10.1097/gco.0b013e328355854d| pmid = 22729095 }}</ref><ref>{{cite journal | vauthors = Lee CN, Lin SY, Lin CH, Shih JC, Lin TH, Su YN|author-link4=Jean Chen Shih | year = 2012 | title = Clinical utility of array comparative genomic hybridization for prenatal diagnosis: a cohort study of 3171 pregnancies | journal = BJOG: An International Journal of Obstetrics & Gynaecology | volume = 119 | issue = 5| pages = 614–625 | doi=10.1111/j.1471-0528.2012.03279.x|pmid=22313859 | doi-access = free }}</ref>