Low risk of embryonic and other cancers in PIK3CA-related overgrowth spectrum: Impact on screening recommendations.
PIK3CA
PIK3CA-related overgrowth spectrum (PROS)
Wilms tumor
cancer
Journal
Clinical genetics
ISSN: 1399-0004
Titre abrégé: Clin Genet
Pays: Denmark
ID NLM: 0253664
Informations de publication
Date de publication:
11 2023
11 2023
Historique:
revised:
07
07
2023
received:
23
12
2022
accepted:
19
07
2023
medline:
3
10
2023
pubmed:
15
8
2023
entrez:
14
8
2023
Statut:
ppublish
Résumé
The PIK3CA-related overgrowth spectrum (PROS) encompasses various conditions caused by mosaic activating PIK3CA variants. PIK3CA somatic variants are also involved in various cancer types. Some generalized overgrowth syndromes are associated with an increased risk of Wilms tumor (WT). In PROS, abdominal ultrasound surveillance has been advocated to detect WT. We aimed to determine the risk of embryonic and other types of tumors in patients with PROS in order to evaluate surveillance relevance. We searched the clinical charts from 267 PROS patients for the diagnosis of cancer, and reviewed the medical literature for the risk of cancer. In our cohort, six patients developed a cancer (2.2%), and Kaplan Meier analyses estimated cumulative probabilities of cancer occurrence at 45 years of age was 5.6% (95% CI = 1.35%-21.8%). The presence of the PIK3CA variant was only confirmed in two out of four tumor samples. In the literature and our cohort, six cases of Wilms tumor/nephrogenic rests (0.12%) and four cases of other cancers have been reported out of 483 proven PIK3CA patients, in particular the p.(His1047Leu/Arg) variant. The risk of WT in PROS being lower than 5%, this is insufficient evidence to recommend routine abdominal imaging. Long-term follow-up studies are needed to evaluate the risk of other cancer types, as well as the relationship with the extent of tissue mosaicism and the presence or not of the variant in the tumor samples.
Substances chimiques
Class I Phosphatidylinositol 3-Kinases
EC 2.7.1.137
PIK3CA protein, human
EC 2.7.1.137
Banques de données
ClinicalTrials.gov
['NCT01950975']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
554-563Informations de copyright
© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Références
Lapunzina P. Risk of tumorigenesis in overgrowth syndromes: a comprehensive review. Am J Med Genet C Semin Med Genet. 2005;137C(1):53-71. doi:10.1002/ajmg.c.30064
Keppler-Noreuil KM, Sapp JC, Lindhurst MJ, et al. Clinical delineation and natural history of the PIK3CA-related overgrowth spectrum. Am J Med Genet A. 2014;164A(7):1713-1733. doi:10.1002/ajmg.a.36552
Porta C, Paglino C, Mosca A. Targeting PI3K/Akt/mTOR signaling in cancer. Front Oncol. 2014;4:64. doi:10.3389/fonc.2014.00064
Vivanco I, Sawyers CL. The phosphatidylinositol 3-kinase AKT pathway in human cancer. Nat Rev Cancer. 2002;2(7):489-501. doi:10.1038/nrc839
Arafeh R, Samuels Y. PIK3CA in cancer: the past 30 years. Semin Cancer Biol. 2019;59:36-49. doi:10.1016/j.semcancer.2019.02.002
Kundu RV, Frieden IJ. Presence of vascular anomalies with congenital hemihypertrophy and Wilms tumor: an evidence-based evaluation. Pediatr Dermatol. 2003;20(3):199-206. doi:10.1046/j.1525-1470.2003.20303.x
Peterman CM, Fevurly RD, Alomari AI, et al. Sonographic screening for Wilms tumor in children with CLOVES syndrome. Pediatr Blood Cancer. 2017;64(12):e26684. doi:10.1002/pbc.26684
Blatt J, Finger M, Price V, Crary SE, Pandya A, Adams DM. Cancer risk in Klippel-Trenaunay syndrome. Lymphat Res Biol. 2019;17(6):630-636. doi:10.1089/lrb.2018.0049
Scott RH, Walker L, Olsen ØE, et al. Surveillance for Wilms tumour in at-risk children: pragmatic recommendations for best practice. Arch Dis Child. 2006;91(12):995-999. doi:10.1136/adc.2006.101295
Gripp KW, Baker L, Kandula V, et al. Nephroblastomatosis or Wilms tumor in a fourth patient with a somatic PIK3CA mutation. Am J Med Genet A. 2016;170(10):2559-2569. doi:10.1002/ajmg.a.37758
Kuentz P, St-Onge J, Duffourd Y, et al. Molecular diagnosis of PIK3CA-related overgrowth spectrum (PROS) in 162 patients and recommendations for genetic testing. Genet Med. 2017;19(9):989-997. doi:10.1038/gim.2016.220
Breslow N, Beckwith JB, Ciol M, Sharples K. Age distribution of Wilms' tumor: report from the National Wilms' Tumor Study. Cancer Res. 1988;48(6):1653-1657.
Breslow N, Olshan A, Beckwith JB, Green DM. Epidemiology of Wilms tumor. Med Pediatr Oncol. 1993;21(3):172-181. doi:10.1002/mpo.2950210305
Rivera MN, Haber DA. Wilms' tumour: connecting tumorigenesis and organ development in the kidney. Nat Rev Cancer. 2005;5(9):699-712. doi:10.1038/nrc1696
Cohen MM. Beckwith-Wiedemann syndrome: historical, clinicopathological, and etiopathogenetic perspectives. Pediatr Dev Pathol. 2005;8(3):287-304. doi:10.1007/s10024-005-1154-9
Tan TY, Amor DJ. Tumour surveillance in Beckwith-Wiedemann syndrome and hemihyperplasia: a critical review of the evidence and suggested guidelines for local practice. J Paediatr Child Health. 2006;42(9):486-490. doi:10.1111/j.1440-1754.2006.00908.x
Brioude F, Lacoste A, Netchine I, et al. Beckwith-Wiedemann syndrome: growth pattern and tumor risk according to molecular mechanism, and guidelines for tumor surveillance. Horm Res Paediatr. 2013;80(6):457-465. doi:10.1159/000355544
Mussa A, Molinatto C, Baldassarre G, et al. Cancer risk in Beckwith-Wiedemann syndrome: a systematic review and meta-analysis outlining a novel (epi)genotype specific histotype targeted screening protocol. J Pediatr. 2016;176:142-149. doi:10.1016/j.jpeds.2016.05.038
Zarate YA, Mena R, Martin LJ, Steele P, Tinkle BT, Hopkin RJ. Experience with hemihyperplasia and Beckwith-Wiedemann syndrome surveillance protocol. Am J Med Genet A. 2009;149A(8):1691-1697. doi:10.1002/ajmg.a.32966
Greene AK, Kieran M, Burrows PE, Mulliken JB, Kasser J, Fishman SJ. Wilms tumor screening is unnecessary in Klippel-Trenaunay syndrome. Pediatrics. 2004;113(4):e326-e329.
Maas SM, Vansenne F, Kadouch DJM, et al. Phenotype, cancer risk, and surveillance in Beckwith-Wiedemann syndrome depending on molecular genetic subgroups. Am J Med Genet A. 2016;170(9):2248-2260. doi:10.1002/ajmg.a.37801
Pastore G, Znaor A, Spreafico F, Graf N, Pritchard-Jones K, Steliarova-Foucher E. Malignant renal tumours incidence and survival in European children (1978-1997): report from the automated childhood cancer information system project. Eur J Cancer. 2006;42(13):2103-2114. doi:10.1016/j.ejca.2006.05.010
Biderman Waberski M, Lindhurst M, Keppler-Noreuil KM, et al. Urine cell-free DNA is a biomarker for nephroblastomatosis or Wilms tumor in PIK3CA-related overgrowth spectrum (PROS). Genet Med. 2018;20(9):1077-1081. doi:10.1038/gim.2017.228
Kim K, Lindstrom MJ, Gould MN. Regions of H- and K-ras that provide organ specificity/potency in mammary cancer induction. Cancer Res. 2002;62(5):1241-1245.
Correa P. Is gastric cancer preventable? Gut. 2004;53(9):1217-1219. doi:10.1136/gut.2004.039834
Chun N, Ford JM. Genetic testing by cancer site: stomach. Cancer J Sudbury Mass. 2012;18(4):355-363. doi:10.1097/PPO.0b013e31826246dc
Shi J, Yao D, Liu W, et al. Highly frequent PIK3CA amplification is associated with poor prognosis in gastric cancer. BMC Cancer. 2012;12:50. doi:10.1186/1471-2407-12-50
Salman SM, Phillips T, Rogers GS. Klippel-Trenaunay syndrome and cutaneous carcinomas. J Dermatol Surg Oncol. 1993;19(6):582-584. doi:10.1111/j.1524-4725.1993.tb00393.x
Tan MH, Mester JL, Ngeow J, Rybicki LA, Orloff MS, Eng C. Lifetime cancer risks in individuals with germline PTEN mutations. Clin Cancer Res. 2012;18(2):400-407. doi:10.1158/1078-0432.CCR-11-2283
Ngeow J, Mester J, Rybicki LA, Ni Y, Milas M, Eng C. Incidence and clinical characteristics of thyroid cancer in prospective series of individuals with Cowden and Cowden-like syndrome characterized by germline PTEN, SDH, or KLLN alterations. J Clin Endocrinol Metab. 2011;96(12):E2063-E2071. doi:10.1210/jc.2011-1616
Madsen RR, Vanhaesebroeck B, Semple RK. Cancer-associated PIK3CA mutations in overgrowth disorders. Trends Mol Med. 2018;24(10):856-870. doi:10.1016/j.molmed.2018.08.003
Mankad VN, Gray GF, Miller DR. Bilateral nephroblastomatosis and Klippel Trenaunay syndrome. Cancer. 1974;33(5):1462-1467. doi:10.1002/1097-0142(197405)33:5<1462::aid-cncr2820330533>3.0.co;2-6
Pendergrass TW. Congenital anomalies in children with Wilms' tumor: a new survey. Cancer. 1976;37(1):403-408. doi:10.1002/1097-0142(197601)37:1<403::aid-cncr2820370152>3.0.co;2-h
Ehrich JH, Ostertag H, Flatz S, Kamran D. Bilateral Wilms's tumour in Klippel-Trenaunay syndrome. Arch Dis Child. 1979;54(5):405. doi:10.1136/adc.54.5.405
Mirzaa G, Timms AE, Conti V, et al. PIK3CA-associated developmental disorders exhibit distinct classes of mutations with variable expression and tissue distribution. JCI Insight. 2016;1(9):87623. doi:10.1172/jci.insight.87623
Postema FAM, Hopman SMJ, Deardorff MA, et al. Nephroblastomatosis or Wilms tumor in a fourth patient with a somatic PIK3CA mutation. Am J Med Genet A. 2017;173(8):2293-2295. doi:10.1002/ajmg.a.38290
Hucthagowder V, Shenoy A, Corliss M, et al. Utility of clinical high-depth next generation sequencing for somatic variant detection in the PIK3CA-related overgrowth spectrum. Clin Genet. 2017;91(1):79-85. doi:10.1111/cge.12819
Howitz P, Howitz J, Gjerris F. A variant of the Klippel-Trenaunay-Weber syndrome with temporal lobe astrocytoma. Acta Paediatr Scand. 1979;68(1):119-121. doi:10.1111/j.1651-2227.1979.tb04971.x
Wirtz P, Steinmeister G, Kummerhoff PW, Haase H. 37-year-old patient with anemia and increasing backache in Klippel-Trenaunay syndrome. Internist. 1993;34(7):678-681.
Aygencel G, Demiroglu H. Hodgkin's disease in a patient with Klippel-Trenaunay syndrome. N Z Med J. 1997;110(1041):133.
Lezama-del Valle P, Gerald WL, Tsai J, Meyers P, La Quaglia MP. Malignant vascular tumors in young patients. Cancer. 1998;83(8):1634-1639. doi:10.1002/(sici)1097-0142(19981015)83:8<1634::aid-cncr20>3.3.co;2-j
Bujanda L, Sánchez A, Vicente JM, et al. Squamous cell carcinoma of the oesophagus in a patient with Klippel-Trenaunay syndrome. Eur J Gastroenterol Hepatol. 2001;13(9):1107-1110. doi:10.1097/00042737-200109000-00019
De Simone C, Giampetruzzi AR, Guerriero C, De Masi M, Amerio P, Cina G. Squamous cell carcinoma arising in a venous ulcer as a complication of the Klippel-Trenaunay syndrome. Clin Exp Dermatol. 2002;27(3):209-211. doi:10.1046/j.1365-2230.2002.01009.x
Fay A, Fynn-Thompson N, Ebb D. Klippel-Trénaunay syndrome and rhabdomyosarcoma in a 3-year-old. Arch Ophthalmol Chic Ill 1960. 2003;121(5):727-729. doi:10.1001/archopht.121.5.727
Chang WC, Hsu HH, Chen CY. Surgical eradication of esophageal carcinoma in a patient with Klippel-Trenaunay syndrome. J Chin Med Assoc. 2004;67(5):252-254.
Mathews MS, Kim RC, Chang GY, Linskey ME. Klippel-Trenaunay syndrome and cerebral haemangiopericytoma: a potential association. Acta Neurochir. 2008;150(4):399-402; discussion 402. doi:10.1007/s00701-008-1550-9
Stephens D, Pillai S, Cham E, Arensman R, Chou P. Serous borderline tumor of the fallopian tube in a patient with Klippel-Trenaunay syndrome. J Pediatr Surg. 2010;45(11):2244-2246. doi:10.1016/j.jpedsurg.2010.06.043
Karunamurthy A, Pantanowitz L, Lepe JG, Reyes-Múgica M. Lethal outcomes in Klippel-Trenaunay syndrome. Pediatr Dev Pathol. 2013;16(5):337-342. doi:10.2350/13-03-1312-OA.1
Yilmaz T, Cikla U, Kirst A, Baskaya MK. Glioblastoma multiforme in Klippel-Trenaunay-weber syndrome: a case report. J Med Case Reports. 2015;9:83. doi:10.1186/s13256-015-0555-2