Medullary thyroid carcinoma identified within the first year of life in children with hereditary multiple endocrine neoplasia type 2A (codon 634) and 2B

Zénaty, Delphine; Aigrain, Y; Peuchmaur, M.; Philippe‐Chomette, Pascale; Baumann, C. A.; Cornélis, François; Hugot, Jean‐Pierre; Chevenne, Didier; Barbu, Véronique; Guillausseau, P. J.; Schlumberger, Martin; Carel, Jean Claude; Travagli, J. P.; Léger, Juliane

doi:10.1530/eje-08-0854

Cited by 62 publications

(17 citation statements)

References 39 publications

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“…Patients with a codon 918 mutation and MEN2B are at high risk of aggressive MTC occurring at a young age (31). In contrast, patients with codon 791 mutations are at a relatively low risk of aggressive disease and develop slow-growing tumors as a late manifestation (27).…”

Section: Introductionmentioning

confidence: 99%

Genotype-phenotype correlation in multiple endocrine neoplasia type 2

Raue¹,

Frank‐Raue²

2012

Clinics

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Multiple endocrine neoplasia type 2 is an autosomal-dominant hereditary cancer syndrome caused by missense gain-of-function mutations of the rearranged during transfection proto-oncogene, which encodes the receptor tyrosine kinase, on chromosome 10. It has a strong penetrance of medullary thyroid carcinomas and can be associated with bilateral pheochromocytoma and primary hyperparathyroidism. Multiple endocrine neoplasia type 2 is divided into three varieties depending on its clinical features: multiple endocrine neoplasia type 2A, multiple endocrine neoplasia type 2B, and familial medullary thyroid carcinoma. The specific rearranged during transfection mutation may suggest a predilection toward a particular phenotype and clinical course of medullary thyroid carcinoma, with strong genotype-phenotype correlations. Offering rearranged during transfection testing is the best practice for the clinical management of patients at risk of developing multiple endocrine neoplasia type 2, and multiple endocrine neoplasia type 2 has become a classic model for the integration of molecular medicine into patient care. Recommendations on the timing of prophylactic thyroidectomy and extent of surgery are based on the classification of rearranged during transfection mutations into risk levels according to genotype-phenotype correlations. Earlier identification of patients with hereditary medullary thyroid carcinoma can change the presentation from clinical tumor to preclinical disease, resulting in a high cure rate of affected patients and a much better prognoses.

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Section: Introductionmentioning

confidence: 99%

Genotype-phenotype correlation in multiple endocrine neoplasia type 2

Raue¹,

Frank‐Raue²

2012

Clinics

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“…Histologically, the tumor was 2.5 mm in size and had infiltrating borders in focal areas, confirming the diagnosis of microscopic MTC and distinguishing it from C-cell hyperplasia [4]. Other reports of early MTC in MEN 2B include a microscopic MTC in a 9-week-old infant, but with a de novo mutation [5], and metastatic MTC in a 3-month-old infant with familial MEN 2B [6]. …”

Section: Discussionmentioning

confidence: 73%

Medullary thyroid cancer in a 9-week-old infant with familial MEN 2B: Implications for timing of prophylactic thyroidectomy

Shankar

Rutter

Chernausek

et al. 2012

Int J Pediatr Endocrinol

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BackgroundPatients with Multiple Endocrine Neoplasia type 2 (MEN 2) are at high risk of developing aggressive medullary thyroid carcinoma (MTC) in childhood, with the highest risk in those with MEN type 2B (of whom >95% have an M918T RET proto-oncogene mutation). Metastatic MTC has been reported as young as 3 months of age. Current guidelines recommend prophylactic thyroidectomy within the first year of life for MEN 2B.Patient findingsWe report a 9-week-old infant with MTC due to familial MEN 2B. A full-term male infant, born to a mother with known MEN 2B and metastatic MTC, had an M918T RET proto-oncogene mutation confirmed at 4 weeks of age. He underwent prophylactic total thyroidectomy at 9 weeks of age. Pathology showed a focal calcitonin-positive nodule (2.5 mm), consistent with microscopic MTC.SummaryThis case highlights the importance of early prophylactic thyroidectomy in MEN 2B. Although current guidelines recommend surgery up to a year of life, MTC may occur in the first few weeks of life, raising the question of how early we should intervene. In this report, we discuss the risks, benefits and barriers to performing earlier thyroidectomy, soon after the first month of life, and make suggestions to facilitate timely intervention. Prenatal anticipatory surgical scheduling could be considered in familial MEN 2B. Multidisciplinary collaboration between adult and pediatric specialists is key to the optimal management of the infant at risk.

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“…Hybridization patterns obtained in the oligoarray with PCR products for healthy subject showing only reaction with wt probes (e); furthermore (f) and (g) hybridization patterns of both MEN2B ssDNA using peripheral blood cells; and h Hybridization pattern of dsDNA (from conventional PCR) from a MEN2B paraffinembedded tissue carcinoma occurs in all patients with MEN2, and it can be lethal. An early diagnosis could mean a better prognosis and achieve the detection of preneoplastic stage disease or microcarcinoma, lymph node involvement, and avoiding making it possible biochemical cure [3,18,24,25]. …”

Section: Resultsmentioning

confidence: 99%

Single oligoarray-based detection of specific M918T mutation in RET oncogene in multiple endocrine neoplasia type 2B

Pacheco-Rivera¹,

Hernández-Zamora

González-Yebra

et al. 2011

Clin Exp Med

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The most important mutation associated with Multiple Endocrine Neoplasia type 2B (MEN 2B) is the change of thymine to cytosine in codon 918 of exon 16 in the RET oncogene (ATG → ACG). The aim of this work was to develop a single oligoarray by using tandem hybridization to detect the T918C/RET mutation for MEN 2B patients. Two genetically non-related families were studied; each family had a member affected by MEN2B. Both patients presented the T918C/RET mutation in a heterozygous fashion. None of the relatives was positive for this mutation; thus, these cases arose de novo. The proper mutation was confirmed by with different tools, PCR-Fok I endonuclease, direct sequencing, and also using our oligoarray. In this case, it is suitable to use a DNA target smaller than 150 bases with single- or double-stranded DNA and short probes of 7-mer. It was also possible to detect the mutation by employing different sources of DNA, fresh or paraffin-embedded tissues. Therefore, the present oligoarray can identify the most common M918T mutation of RET oncogene from a variety of DNA sources with good specificity and be a good alternative in the molecular diagnosis for MEN 2B cases.

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Medullary thyroid carcinoma identified within the first year of life in children with hereditary multiple endocrine neoplasia type 2A (codon 634) and 2B

Cited by 62 publications

References 39 publications

Genotype-phenotype correlation in multiple endocrine neoplasia type 2

Genotype-phenotype correlation in multiple endocrine neoplasia type 2

Medullary thyroid cancer in a 9-week-old infant with familial MEN 2B: Implications for timing of prophylactic thyroidectomy

Single oligoarray-based detection of specific M918T mutation in RET oncogene in multiple endocrine neoplasia type 2B

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