Chorangioma (CA) is the most common nontrophoblastic, vascular tumor-like lesion of the placenta with a reported incidence of 0.5% to 1% in all examined placentas. The underlying molecular mechanisms of CAs are still poorly elucidated, and a systematic investigation of the genetic background of CAs has not previously been done.
Materials and Methods
Tissue biopsies from 8 large (>40 mm) histologically confirmed CAs and 8 unaffected matched placenta controls, along with standard control DNA samples were analyzed for large genomic deletions and duplications using array comparative genomic hybridization (array-CGH) method.
Results
Array-CGH analysis revealed no rare or novel copy number variants in the CA samples compared with either standard control DNA or unaffected placenta DNA from the same individual.
Discussion
In this study, a systematic genetic investigation of 8 large CAs failed to demonstrate any large-scale pathogenic genetic changes. This lack of association might support a nongenetic, nontumorous origin of these lesions; however, additional genetic studies focusing on smaller genomic alterations are required to fully assess any possible genetic contribution.
FoxHSebireNJ. Pathology of the Placenta., 3rd ed. Philadelphia, PA: Saunders Elsevier, 2007, pp. 402.
2.
AmerHZHellerDS. Chorangioma and related vascular lesions of the placenta—a review. Fetal Pediatr Pathol2010; 29: 199–206.
3.
SirotkinaMDouroudisKPapadogiannakisNWestgrenM. Clinical outcome in singleton and multiple pregnancies with placental chorangioma. PLoS One2016; 11(11): e0166562.
4.
FanMSkupskiDW. Placental chorioangioma: literature review. J Perinat Med2014; 42: 273–279.
5.
OginoSRedlineRW. Villous capillary lesions of the placenta: distinctions between chorangioma, chorangiomatosis, and chorangiosis. Hum Pathol2000; 31: 945–954.
6.
BenirschkeK. Recent trends in chorangiomas, especially those of multiple and recurrent chorangiomas. Pediatr Dev Pathol1999; 2: 264–269.
7.
MiliarasDConroyJPervanaSMeditskouSMcQuaidDNowakN. Karyotypic changes detected by comparative genomic hybridization in stillborn infant with chorionangioma and liver hemangioma. Birth Defects Res A Clin Mol Teratol2007; 79: 236–241.
8.
KimCKBenirschkeKConnollyKS. Chorangioma of the placenta: chromosomal and electron microscopic studies. Obstet Gynecol1971; 37: 372–376.
9.
PetterssonMViljakainenHLoidPet al.Copy number variants are enriched in individuals with early-onset obesity and highlight novel pathogenic pathways. J Clin Endocrinol Metab2017; 102: 3029–3039.
10.
Kearney HM, Thorland EC, Brown KK, Quintero-Rivera F, South ST; Working Group of the American College of Medical Genetics Laboratory Quality Assurance Committee. American College of Medical Genetics standards and guidelines for interpretation and reporting of postnatal constitutional copy number variants. Genet Med. 2011;13(7):680–685.
11.
WursterDHHoefnagelDBenirschkeKAllenFHJr. Placental chorangiomata and mental deficiency in a child with 2/15 translocation: 46,XX,t(2q−;15q+). Cytogenetics1969; 8: 389–399.
12.
BlattJPowellCMBurkhartCNStavasJAylsworthAS. Genetics of hemangiomas, vascular malformations, and primary lymphedema. J Pediatr Hematol Oncol2014; 36: 587–593.
13.
HoegerPHMaerkerJMKienastAKSyedSBHarperJI. Neonatal haemangiomatosis associated with placental chorioangiomas: report of three cases and review of the literature. Clin Exp Dermatol2009; 34: 78–80.
14.
AyturkUMCoutoJAHannSet al.Somatic activating mutations in GNAQ and GNA11 are associated with congenital hemangioma. Am J Hum Genet2016; 98: 789–795.
15.
FunkTLimYKulungowskiAMet al.Symptomatic congenital hemangioma and congenital hemangiomatosis associated with a somatic activating mutation in GNA11. JAMA Dermatol2016; 152: 1015–1020.
16.
Wooderchak-DonahueWLMcDonaldJO'FallonBet al.BMP9 mutations cause a vascular-anomaly syndrome with phenotypic overlap with hereditary hemorrhagic telangiectasia. Am J Hum Genet2013; 93: 530–537.
17.
JohnsonDWBergJNBaldwinMAet al.Mutations in the activin receptor-like kinase 1 gene in hereditary haemorrhagic telangiectasia type 2. Nat Genet1996; 13: 189–195.
18.
JinninMMediciDParkLet al.Suppressed NFAT-dependent VEGFR1 expression and constitutive VEGFR2 signaling in infantile hemangioma. Nat Med2008; 14: 1236–1246.
19.
JiaoWVembuSDeshwarAGSteinLMorrisQ. Inferring clonal evolution of tumors from single nucleotide somatic mutations. BMC Bioinformatics2014; 1: 15–35.
20.
VisvaderJE. Cells of origin in cancer. Nature2011; 469: 314–322.
21.
McGranahanNSwantonC. Clonal heterogeneity and tumor evolution: past, present, and the future. Cell2017; 168: 613–628.
22.
GreavesM. Evolutionary determinants of cancer. Cancer Discov2015; 5: 806–820.
23.
VissersLEVeltmanJAvan KesselAGBrunnerHG. Identification of disease genes by whole genome CGH arrays. Hum Mol Genet2005; 14: R215–R223.
24.
SebatJLakshmiBTrogeJet al.Large-scale copy number polymorphism in the human genome. Science2004; 305: 525–528.
25.
PinkelDSegravesRSudarDet al.High resolution analysis of DNA copy number variation using comparative genomic hybridization to microarrays. Nature Genet1998; 20: 207–211.
26.
AlvarezCAravenaATapiaTet al.Different Array CGH profiles within hereditary breast cancer tumors associated to BRCA1 expression and overall survival. BMC Cancer2016; 16: 219.
27.
Shaw-SmithCRedonRRickmanLet al.Microarray-based comparative genomic hybridisation (array-CGH) detects submicroscopic chromosomal deletions and duplications in patients with learning disability/mental retardation and dysmorphic features. J Med Genet2004; 41: 241–248.
28.
LuXYPhungMTShawCAet al.Genomic imbalances in neonates with birth defects: high detection rates by using chromosomal microarray analysis. Pediatrics2008; 122: 1310–1318.
29.
IafrateAJFeukLRiveraMNet al.Detection of large-scale variation in the human genome. Nat Genet2004; 36: 949–951.
30.
ConradDFPintoDRedonRet al.Origins and functional impact of copy number variation in the human genome. Nature2010; 464: 704–712.
31.
ManolioTA. Genome wide association studies and assessment of the risk of disease. N Engl J Med2010; 363: 166–176.
32.
KumaranMCassCEGrahamKet al.Germline copy number variations are associated with breast cancer risk and prognosis. Sci Rep2017; 7: 14621.
33.
ManolioTACollinsFSCoxNJet al.Finding the missing heritability of complex diseases. Nature2009; 461: 747–753.
34.
López GutiérrezJCAvilaLFSosaGPatronM. Placental anomalies in children with infantile hemangioma. Pediatr Dermatol2007; 24: 353–355.
