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Familial medullary carcinoma prevention, risk evaluation, and RET in children of families with MEN2.
J Pediatr Surg. 2007 Feb; 42(2):326-32.JP

Abstract

The ability to predict the risk of MEN2 and medullary thyroid carcinoma (MTC) by genetic RET proto-oncogene analysis has provided an essential tool in identifying patients in whom thyroid cancer can be prevented by prophylactic thyroidectomy but emphasizes the need for clear policy guidelines. Children of families with RET cysteine mutations (exons 10, 11, 13, and 16) may develop early metastatic tumours and require prophylactic thyroidectomy. The 918 mutation associated with MEN2B is associated with early aggressive behaviour and distant metastatic spread. This has led to active screening of affected families underlining the need for specific intervention strategies.

AIM

To evaluate the risk to children of families with MEN2 and to assess the risk and determine the treatment.

METHODS

Twenty-five patients from 10 families with MEN2 phenotypes were screened for RET mutations. Polymerase chain reaction amplification was performed on all 21 exons of the RET proto-oncogene, followed by heteroduplex single-strand conformation polymorphism (HEX-SSCP) analysis. Polymerase chain reaction products demonstrating variation in the HEX-SSCP gels were subjected to automated DNA sequencing analysis.

RESULTS

Eleven significant RET mutations were detected in affected families. Eight index cases received initial thyroidectomy for established MTC (plus 2 advised). In the family members screened, 3 prophylactic thyroidectomies (2 with early MTC) were performed and a further 2 recommended. An exon 10 C620W missense mutation (the "Janus" gene) was detected in a patient with Hirschsprung's disease plus 1 family member.

CONCLUSION

RET analysis of MEN has revolutionized the management of children of families with MEN2 and allowed surgical prediction and prophylaxis to take place. The presence of an exon 10 C620W mutation in association with Hirschsprung's disease was difficult to assess. We suggest possible guidelines for management of families with MTC and the role of genetic testing in their evaluation.

Authors+Show Affiliations

Department of Pediatric Surgery, University of Stellenbosch Medical Faculty, PO Box 19063, Tygerberg 7505, South Africa. swm@sun.ac.zaNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

17270543

Citation

Moore, Samuel W., et al. "Familial Medullary Carcinoma Prevention, Risk Evaluation, and RET in Children of Families With MEN2." Journal of Pediatric Surgery, vol. 42, no. 2, 2007, pp. 326-32.
Moore SW, Appfelstaedt J, Zaahl MG. Familial medullary carcinoma prevention, risk evaluation, and RET in children of families with MEN2. J Pediatr Surg. 2007;42(2):326-32.
Moore, S. W., Appfelstaedt, J., & Zaahl, M. G. (2007). Familial medullary carcinoma prevention, risk evaluation, and RET in children of families with MEN2. Journal of Pediatric Surgery, 42(2), 326-32.
Moore SW, Appfelstaedt J, Zaahl MG. Familial Medullary Carcinoma Prevention, Risk Evaluation, and RET in Children of Families With MEN2. J Pediatr Surg. 2007;42(2):326-32. PubMed PMID: 17270543.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Familial medullary carcinoma prevention, risk evaluation, and RET in children of families with MEN2. AU - Moore,Samuel W, AU - Appfelstaedt,Justus, AU - Zaahl,Monique G, PY - 2007/2/3/pubmed PY - 2007/2/23/medline PY - 2007/2/3/entrez SP - 326 EP - 32 JF - Journal of pediatric surgery JO - J Pediatr Surg VL - 42 IS - 2 N2 - UNLABELLED: The ability to predict the risk of MEN2 and medullary thyroid carcinoma (MTC) by genetic RET proto-oncogene analysis has provided an essential tool in identifying patients in whom thyroid cancer can be prevented by prophylactic thyroidectomy but emphasizes the need for clear policy guidelines. Children of families with RET cysteine mutations (exons 10, 11, 13, and 16) may develop early metastatic tumours and require prophylactic thyroidectomy. The 918 mutation associated with MEN2B is associated with early aggressive behaviour and distant metastatic spread. This has led to active screening of affected families underlining the need for specific intervention strategies. AIM: To evaluate the risk to children of families with MEN2 and to assess the risk and determine the treatment. METHODS: Twenty-five patients from 10 families with MEN2 phenotypes were screened for RET mutations. Polymerase chain reaction amplification was performed on all 21 exons of the RET proto-oncogene, followed by heteroduplex single-strand conformation polymorphism (HEX-SSCP) analysis. Polymerase chain reaction products demonstrating variation in the HEX-SSCP gels were subjected to automated DNA sequencing analysis. RESULTS: Eleven significant RET mutations were detected in affected families. Eight index cases received initial thyroidectomy for established MTC (plus 2 advised). In the family members screened, 3 prophylactic thyroidectomies (2 with early MTC) were performed and a further 2 recommended. An exon 10 C620W missense mutation (the "Janus" gene) was detected in a patient with Hirschsprung's disease plus 1 family member. CONCLUSION: RET analysis of MEN has revolutionized the management of children of families with MEN2 and allowed surgical prediction and prophylaxis to take place. The presence of an exon 10 C620W mutation in association with Hirschsprung's disease was difficult to assess. We suggest possible guidelines for management of families with MTC and the role of genetic testing in their evaluation. SN - 1531-5037 UR - https://www.unboundmedicine.com/medline/citation/17270543/Familial_medullary_carcinoma_prevention_risk_evaluation_and_RET_in_children_of_families_with_MEN2_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0022-3468(06)00763-9 DB - PRIME DP - Unbound Medicine ER -