Abstract
Array-based comparative genomic hybridization (aCGH) is a powerful assay to identify copy number abnormalities underlying the pathogenesis of cancer. aCGH has become the gold standard for whole genome copy number analysis in medium and large cohorts in clinical and research laboratories. Identifying the best workflow is critical to achieving the optimal performance for this assay. Here we describe the aCGH protocol used by our group in the study of B-chronic lymphocytic leukemia (CLL). We also describe some initial applications of aCGH in association with clinical outcome for CLL.
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References
Redon R, Ishikawa S, Fitch KR et al (2006) Global variation in copy number in the human genome. Nature 444(7118):444–454
Mccarroll SA, Kuruvilla FG, Korn JM et al (2008) Integrated detection and population-genetic analysis of snps and copy number variation. Nat Genet 40(10):1166–1174
Lee JA, Lupski JR (2006) Genomic rearrangements and gene copy-number alterations as a cause of nervous system disorders. Neuron 52(1):103–121
Veltman JA, Jonkers Y, Nuijten I et al (2003) Definition of a critical region on chromosome 18 for congenital aural atresia by arraycgh. Am J Hum Genet 72(6):1578–1584
Braggio E, Keats JJ, Leleu X et al (2009) Identification of copy number abnormalities and inactivating mutations in two negative regulators of nuclear factor-kappab signaling pathways in waldenstrom’s macroglobulinemia. Cancer Res 69(8):3579–3588
Keats JJ, Fonseca R, Chesi M et al (2007) Promiscuous mutations activate the noncanonical nf-kappab pathway in multiple myeloma. Cancer Cell 12(2):131–144
Mao X, Orchard G, Lillington DM et al (2003) Amplification and overexpression of junb is associated with primary cutaneous t-cell lymphomas. Blood 101(4):1513–1519
Mullighan CG, Goorha S, Radtke I et al (2007) Genome-wide analysis of genetic alterations in acute lymphoblastic leukaemia. Nature 446(7137):758–764
Clark J, Edwards S, Feber A et al (2003) Genome-wide screening for complete genetic loss in prostate cancer by comparative hybridization onto cdna microarrays. Oncogene 22(8):1247–1252
Martinez-Climent JA, Alizadeh AA, Segraves R et al (2003) Transformation of follicular lymphoma to diffuse large cell lymphoma is associated with a heterogeneous set of DNA copy number and gene expression alterations. Blood 101(8):3109–3117
Pollack JR, Sorlie T, Perou CM et al (2002) Microarray analysis reveals a major direct role of DNA copy number alteration in the transcriptional program of human breast tumors. Proc Natl Acad Sci USA 99(20):12963–12968
Edwards JH, Harnden DG, Cameron AH et al (1960) A new trisomic syndrome. Lancet 1(7128):787–790
Lejeune J, Turpin R, Gautier M (1959) Mongolism; a chromosomal disease (trisomy). Bull Acad Natl Med 143(11–12):256–265
Weiss LA, Shen Y, Korn JM et al (2008) Association between microdeletion and microduplication at 16p11.2 and autism. N Engl J Med 358(7):667–675
Pollack JR, Perou CM, Alizadeh AA et al (1999) Genome-wide analysis of DNA copy-number changes using cdna microarrays. Nat Genet 23(1):41–46
Albertson DG, Pinkel D (2003) Genomic microarrays in human genetic disease and cancer. Hum Mol Genet 12 Spec No 2:R145–R152
Metzker ML (2010) Sequencing technologies—the next generation. Nat Rev Genet 11:31–46
Stilgenbauer S, Bullinger L, Lichter P et al (2002) Genetics of chronic lymphocytic leukemia: genomic aberrations and v(h) gene mutation status in pathogenesis and clinical course. Leukemia 16(6):993–1007. doi:10.1038/sj.leu.2402537
Dohner H, Stilgenbauer S, Benner A et al (2000) Genomic aberrations and survival in chronic lymphocytic leukemia. N Engl J Med 343(26):1910–1916. doi:MJBA-432602 [pii] 10.1056/NEJM200012283432602
Kay NE, Eckel-Passow JE, Braggio E et al (2011) Progressive but previously untreated CLL patients with greater array CGH complexity exhibit a less durable response to chemoimmunotherapy. Cancer Genet Cytogenet 203(2):161–168. doi:S0165-4608(10)00492-9 [pii] 10.1016/j.cancergencyto.2010.09.003
Ouillette P, Collins R, Shakhan S et al (2011) Acquired genomic copy number aberrations and survival in chronic lymphocytic leukemia. Blood 118(11):3051–3061. doi:blood-2010-12-327858 [pii] 10.1182/blood-2010-12-327858
Braggio E, Kay NE, Vanwier S, Tschumper RC, Smoley S, Eckel-Passow JE, et al (2012) Longitudinal genome-wide analysis of patients with chronic lymphocytic leukemia reveals complex evolution of clonal architecture at disease progression and at the time of relapse. Leukemia 26(7):1698–1701blood-2010-12-327858 [pii] 10.1182/blood-2010-12-327858
Knight SJ, Yau C, Clifford R, Timbs AT, Sadighi Akha E, Dréau HM, Burns A, Ciria C, Oscier DG, Pettitt AR, Dutton S, Holmes CC, Taylor J, Cazier JB, Schuh A (2012) Quantification of subclonal distributions of recurrent genomic aberrations in paired pre-treatment and relapse samples from patients with B-cell chronic lymphocytic leukemia. Leukemia 26(7):1564–1575
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Braggio, E., Fonseca, R., Kay, N.E. (2013). CGH Protocols: Chronic Lymphocytic Leukemia. In: Banerjee, D., Shah, S. (eds) Array Comparative Genomic Hybridization. Methods in Molecular Biology, vol 973. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-281-0_6
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DOI: https://doi.org/10.1007/978-1-62703-281-0_6
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