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J Zhejiang Univ (Med Sci)  2019, Vol. 48 Issue (5): 560-566    DOI: 10.3785/j.issn.1008-9292.2019.10.15
Research progress on uniparental disomy in cancer
CHEN Dianyu1,2(),QI Ming1,2,3,*()
1. Department of Genetics, Zhejiang University School of Medicine, Hangzhou 310058, China
2. International Precision Medicine Research Center, Zhejiang-California International Nanosystems Institute, Hangzhou 310058, China
3. Di'an Diagnostics, Hangzhou 310030, China
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Uniparental disomy (UPD) refers to a chromosome defect that an individual's homologous chromosome or segments are inherited from one parent. UPD can cause either aberrant patterns of genomic imprinting or homozygosity of mutations, leading to various diseases, including cancer. The mechanisms of UPD formation are diverse but largely due to the incorrect chromosome separation during cell division. UPD does not alter the number of gene copies, thus is difficult to be detected by conventional cytogenetic techniques effectively. Assisted by the new techniques such as single nucleotide polymorphism arrays, more and more UPD-related cases have been reported recently. UPD events are non-randomly distributed across cancer types, which play important role in the occurrence, development and metastasis of cancer. Here we review the research progress on the formation mechanisms, detection methods, the involved chromosomal regions and genes, and clinical significance of UPD; and also discuss the directions for future studies in this field.

Key wordsNeoplasms      Uniparental disomy      Polymorphism, single nucleotide      Chromosome aberrations      Oncogenes      Genes, tumor suppressor      Review     
Received: 12 March 2019      Published: 04 January 2020
CLC:  R394.3  
Corresponding Authors: QI Ming     E-mail:;
Cite this article:

CHEN Dianyu,QI Ming. Research progress on uniparental disomy in cancer. J Zhejiang Univ (Med Sci), 2019, 48(5): 560-566.

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关键词: 肿瘤,  单亲二体性,  多态性, 单核苷酸,  染色体畸变,  癌基因,  基因, 肿瘤抑制,  综述 
[1]   ENGEL E . A new genetic concept: uniparental disomy and its potential effect, isodisomy[J]. Am J Med Genet, 1980, 6 (2): 137- 143
[2]   SPENCE J E , PERCIACCANTE R G , GREIG G M et al. Uniparental disomy as a mechanism for human genetic disease[J]. Am J Hum Genet, 1988, 42 (2): 217- 226
[3]   MATSUBARA K , KAGAMI M , FUKAMI M . Uniparental disomy as a cause of pediatric endocrine disorders[J]. Clin Pediatr Endocrinol, 2018, 27 (3): 113- 121
[4]   SONG Q , CHU Y , YAO Y et al. Identify latent chromosomal aberrations relevant to myelodysplastic syndromes[J]. Sci Rep, 2017, 7 (1): 10354
[5]   DINIZ M G , DUARTE A P , VILLACISR A et al. Rare copy number alterations and copy-neutral loss of heterozygosity revealed in ameloblastomas by high-density whole-genome microarray analysis[J]. J Oral Pathol Med, 2017, 46 (5): 371- 376
doi: 10.1111/jop.12505
[6]   SANTORO S L , HASHIMOTO S , MCKINNEY A et al. Assessing the clinical utility of SNP microarray for Prader-Willi syndrome due to uniparental disomy[J]. Cytogenet Genome Res, 2017, 152 (2): 105- 109
doi: 10.1159/000478921
[7]   EROLA P , TORABI K , MIRó R et al. The non-random landscape of somatically-acquired uniparental disomy in cancer[J]. Oncotarget, 2019, 10 (40): 3982- 3984
[8]   TUCCI V , ISLES A R , KELSEY G et al. Genomic imprinting and physiological processes in mammals[J]. Cell, 2019, 176 (5): 952- 965
doi: 10.1016/j.cell.2019.01.043
[9]   YAMAZAWA K , OGATA T , FERGUSON-SMITH A C . Uniparental disomy and human disease: an overview[J]. Am J Med Genet C Semin Med Genet, 2010, 154C (3): 329- 334
doi: 10.1002/ajmg.c.30270
[10]   BRIOUDE F , KALISH J M , MUSSA A et al. Expert consensus document: Clinical and molecular diagnosis, screening and management of Beckwith-Wiedemann syndrome: an international consensus statement[J]. Nat Rev Endocrinol, 2018, 14 (4): 229- 249
doi: 10.1038/nrendo.2017.166
[11]   SU L , LU Z , LI F et al. Two homozygous mutations in the exon 5 of BCKDHB gene that may cause the classic form of maple syrup urine disease[J]. Metab Brain Dis, 2017, 32 (3): 765- 772
doi: 10.1007/s11011-017-9959-6
[12]   BIS D M , SCHVLE R , REICHBAUER J et al. Uniparental disomy determined by whole-exome sequencing in a spectrum of rare motoneuron diseases and ataxias[J]. Mol Genet Genomic Med, 2017, 5 (3): 280- 286
doi: 10.1002/mgg3.285
[13]   MAKISHIMA H , MACIEJEWSKI J P . Pathogenesis and consequences of uniparental disomy in cancer[J]. Clin Cancer Res, 2011, 17 (12): 3913- 3923
doi: 10.1158/1078-0432.CCR-10-2900
[14]   LALOU I , GKROZOU F , MERIDIS E et al. Molecular investigation of uniparental disomy (UPD) in spontaneous abortions[J]. Eur J Obstet Gynecol Reprod Biol, 2019, 236 116- 120
doi: 10.1016/j.ejogrb.2019.03.004
[15]   JOSHI R S , GARG P , ZAITLEN N et al. DNA methylation profiling of uniparental disomy subjects provides a map of parental epigenetic bias in the human genome[J]. Am J Hum Genet, 2016, 99 (3): 555- 566
doi: 10.1016/j.ajhg.2016.06.032
[16]   KING D A , FITZGERALD T W , MILLER R et al. A novel method for detecting uniparental disomy from trio genotypes identifies a significant excess in children with developmental disorders[J]. Genome Res, 2014, 24 (4): 673- 687
[17]   TUNA M , KNUUTILA S , MILLS G B . Uniparental disomy in cancer[J]. Trends Mol Med, 2009, 15 (3): 120- 128
doi: 10.1016/j.molmed.2009.01.005
[18]   WANG L , WHEELER D A , PRCHAL J T . Acquired uniparental disomy of chromosome 9p in hematologic malignancies[J]. Exp Hematol, 2016, 44 (8): 644- 652
doi: 10.1016/j.exphem.2015.11.005
[19]   KANAGAL-SHAMANNA R , HODGE J C , TUCKER T et al. Assessing copy number aberrations and copy neutral loss of heterozygosity across the genome as best practice: An evidence based review of clinical utility from the cancer genomics consortium (CGC) working group for myelodysplastic syndrome, myelodysplastic/myeloproliferative and myelo-proliferative neoplasms[J]. Cancer Genet, 2018, 228-229 197- 217
doi: 10.1016/j.cancergen.2018.07.003
[20]   GAYMES T J , MOHAMEDALI A , EILIAZADEH A L et al. FLT3 and JAK2 mutations in acute myeloid leukemia promote interchromosomal homologous recombination and the potential for copy neutral loss of heterozygosity[J]. Cancer Res, 2017, 77 (7): 1697- 1708
doi: 10.1158/0008-5472.CAN-16-1678
[21]   KIMURA S , HASEGAWA D , YOSHIMOTO Y et al. Duplication of ALK F1245 missense mutation due to acquired uniparental disomy associated with aggressive progression in a patient with relapsed neuroblastoma[J]. Oncol Lett, 2019, 17 (3): 3323- 3329
[22]   TAKADA M , NAGAI S , HARUTA M et al. BRCA1 alterations with additional defects in DNA damage response genes may confer chemoresistance to BRCA-like breast cancers treated with neoadjuvant chemotherapy[J]. Genes Chromosomes Cancer, 2017, 56 (5): 405- 420
[23]   RICHARDSON A L , WANG Z C , DE NICOLO A et al. X chromosomal abnormalities in basal-like human breast cancer[J]. Cancer Cell, 2006, 9 (2): 121- 132
doi: 10.1016/j.ccr.2006.01.013
[24]   WALSH C S , OGAWA S , SCOLES D R et al. Genome-wide loss of heterozygosity and uniparental disomy in BRCA1/2-associated ovarian carcinomas[J]. Clin Cancer Res, 2008, 14 (23): 7645- 7651
doi: 10.1158/1078-0432.CCR-08-1291
[25]   TUNA M , AMOS C I , MILLSG B . Genome-wide analysis of head and neck squamous cell carcinomas reveals HPV, TP53, smoking and alcohol-related allele-based acquired uniparental disomy genomic alterations[J]. Neoplasia, 2019, 21 (2): 197- 205
doi: 10.1016/j.neo.2018.12.002
[26]   TORABI K , EROLA P , ALVAREZ-MORAM I et al. Quantitative analysis of somatically acquired and constitutive uniparental disomy in gastrointestinal cancers[J]. Int J Cancer, 2019, 144 (3): 513- 524
[27]   ALEKSEEVA E A , KUZNETSOVA E B , TANAS A S et al. Loss of heterozygosity and uniparental disomy of chromosome region 10q23.3-26.3 in glioblastoma[J]. Genes Chromosomes Cancer, 2018, 57 (1): 42- 47
[28]   TORABI K , MIRó R , FERNáNDEZ-JIMéNEZ N et al. Patterns of somatic uniparental disomy identify novel tumor suppressor genes in colorectal cancer[J]. Carcinogenesis, 2015, 36 (10): 1103- 1110
doi: 10.1093/carcin/bgv115
[29]   KRALOVICS R , GUAN Y , PRCHAL J T . Acquired uniparental disomy of chromosome 9p is a frequent stem cell defect in polycythemia vera[J]. Exp Hematol, 2002, 30 (3): 229- 236
doi: 10.1016/S0301-472X(01)00789-5
[30]   KRALOVICS R , BUSER A S , TEO S S et al. Comparison of molecular markers in a cohort of patients with chronic myeloproliferative disorders[J]. Blood, 2003, 102 (5): 1869- 1871
doi: 10.1182/blood-2003-03-0744
[31]   KRALOVICS R , PASSAMONTI F , BUSERA S et al. A gain-of-function mutation of JAK2 in myeloproliferative disorders[J]. N Engl J Med, 2005, 352 (17): 1779- 1790
doi: 10.1056/NEJMoa051113
[32]   RAGHAVAN M , LILLINGTON D M , SKOULAKIS S et al. Genome-wide single nucleotide polymorphism analysis reveals frequent partial uniparental disomy due to somatic recombination in acute myeloid leukemias[J]. Cancer Res, 2005, 65 (2): 375- 378
[33]   SERRANO E , CARNICER M J , ORANTES V et al. Uniparental disomy may be associated with microsatellite instability in acute myeloid leukemia (AML) with a normal karyotype[J]. Leuk Lymphoma, 2008, 49 (6): 1178- 1183
[34]   GUPTA M , RAGHAVAN M , GALER E et al. Novel regions of acquired uniparental disomy discovered in acute myeloid leukemia[J]. Genes Chromosomes Cancer, 2008, 47 (9): 729- 739
doi: 10.1002/gcc.20573
[35]   FANG M , TOHER J , MORGAN M et al. Genomic differences between estrogen receptor (ER)-positive and ER-negative human breast carcinoma identified by single nucleotide polymorphism array comparative genome hybridization analysis[J]. Cancer, 2011, 117 (10): 2024- 2034
doi: 10.1002/cncr.25770
[36]   TUNA M, SMID M, ZHU D, et al. Association between acquired uniparental disomy and homozygous mutations and HER2/ER/PR status in breast cancer[J/OL]. PLoS One, 2010, 5(11): e15094.
[37]   TUNA M , JU Z , SMID M et al. Prognostic relevance of acquired uniparental disomy in serous ovarian cancer[J]. Mol Cancer, 2015, 14 29
doi: 10.1186/s12943-015-0289-1
[38]   HOLZMANN C , KOCZAN D , LOENING T et al. Case report: a low-grade uterine leiomyosarcoma showing multiple genetic aberrations including a bi-allelic loss of the retinoblastoma gene locus, as well as germ-line uniparental disomy for part of the long arm of chromosome 22[J]. Anticancer Res, 2017, 37 (5): 2233- 2237
doi: 10.21873/anticanres.11559
[39]   KANEKO Y , OKITA H , HARUTA M et al. A high incidence of WT1 abnormality in bilateral Wilms tumours in Japan, and the penetrance rates in children with WT1 germline mutation[J]. Br J Cancer, 2015, 112 (6): 1121- 1133
doi: 10.1038/bjc.2015.13
[40]   DE NORONHA T R , MITNE-NETO M , CHAUFFAILLEM L . Mutational profiling of acute myeloid leukemia with normal cytogenetics in Brazilian patients: the value of next-generation sequencing for genomic classification[J]. J Investig Med, 2017, 65 (8): 1155- 1158
doi: 10.1136/jim-2017-000566
[41]   LEHMANN S , OGAWA S , RAYNAUDS D et al. Molecular allelokaryotyping of early-stage, untreated chronic lymphocytic leukemia[J]. Cancer, 2008, 112 (6): 1296- 1305
doi: 10.1002/cncr.23270
[42]   TUNA M , SMID M , MARTENS J W et al. Prognostic value of acquired uniparental disomy (aUPD) in primary breast cancer[J]. Breast Cancer Res Treat, 2012, 132 (1): 189- 196
[43]   GRONSETH C M , MCELHONE S E , STORER B E et al. Prognostic significance of acquired copy-neutral loss of heterozygosity in acute myeloid leukemia[J]. Cancer, 2015, 121 (17): 2900- 2908
doi: 10.1002/cncr.29475
[44]   BULLINGER L , KR?NKE J , SCH?N C et al. Identification of acquired copy number alterations and uniparental disomies in cytogenetically normal acute myeloid leukemia using high-resolution single-nucleotide polymorphism analysis[J]. Leukemia, 2010, 24 (2): 438- 449
doi: 10.1038/leu.2009.263
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