Four cases of medullary thyroid carcinomas associated with multiple endocrine neoplasia 2B with rearranged during transfection codon M918T mutation in the same family

Tanaka,Akihisa; Uemura,Hirokazu; Morimoto,Chihiro; Nishimura,Ari; Yoshii,Yumi; Masui,Takashi; Ota,Ichiro; Kitahara,Tadashi

doi:10.3892/mco.2021.2450

Four cases of medullary thyroid carcinomas associated with multiple endocrine neoplasia 2B with rearranged during transfection codon M918T mutation in the same family

Authors:
- Akihisa Tanaka
- Hirokazu Uemura
- Chihiro Morimoto
- Ari Nishimura
- Yumi Yoshii
- Takashi Masui
- Ichiro Ota
- Tadashi Kitahara
View Affiliations

Affiliations: Department of Otolaryngology‑Head and Neck Surgery, Nara Medical University, Kashihara, Nara 634‑8522, Japan, Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Sunto‑Gun, Shizuoka 411‑8777, Japan, Departments of Cancer Genomics and Medical Oncology, Nara Medical University, Kashihara, Nara 634‑8522, Japan
Published online on: November 21, 2021 https://doi.org/10.3892/mco.2021.2450
Article Number: 13

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Multiple endocrine neoplasia (MEN) with medullary thyroid carcinoma (MTC) is associated with rearranged during transfection (RET) mutations. The authors encountered four cases of MTC‑related MEN type 2B (MEN2B) with RET codon M918T mutation in one family. Case 1 included a 19 year‑old male diagnosed with MTC with lung metastases. Genetic testing revealed an RET codon M918T mutation, which indicated MEN2B. The patient responded partially to vandetanib and the disease has shown no progression in 25 months. Case 2 involved the mother of the patient in Case 1. She underwent total thyroidectomy (TT) when diagnosed with MTC‑related MEN2B at 12 years of age, but was not counseled adequately. Cases 3 and 4 involved the sisters of the Case 1 patient and were assessed after Case 1 was diagnosed. Genetic testing revealed the same mutation. Case 3 was diagnosed with MTC and underwent TT. Case 4 was asymptomatic but underwent prophylactic TT; histopathologic examination revealed MTC tissue. Prophylactic TT prevented MTC from being detected at an advanced state. Genetic counseling is essential in treating MEN2B. The mother was uninformed about the genetic characteristics of MEN2B, delaying the detection of MTC in her children. The present study reaffirms the importance of family history and screening.

View Figures

View References

1	Lim H, Devesa SS, Sosa JA, Check D and Kitahara CM: Trends in thyroid cancer incidence and mortality in the United States, 1974-2013. JAMA. 317:1338–1348. 2017.PubMed/NCBI View Article : Google Scholar
2	Donis-Keller H, Dou S, Chi D, Carlson KM, Toshima K, Lairmore TC, Howe JR, Moley JF, Goodfellow P and Wells SA Jr: Mutations in the RET proto-oncogene are associated with MEN 2A and FMTC. Hum Mol Genet. 2:851–856. 1993.PubMed/NCBI View Article : Google Scholar
3	Mulligan LM, Kwok JB, Healey CS, Elsdon MJ, Eng C, Gardner E, Love DR, Mole SE, Moore JK, Papi L, et al: Germ-line mutations of the RET proto-oncogene in multiple endocrine neoplasia type 2A. Nature. 363:458–460. 1993.PubMed/NCBI View Article : Google Scholar
4	Carlson KM, Dou S, Chi D, Scavarda N, Toshima K, Jackson CE, Wells SA Jr, Goodfellow PJ and Donis-Keller H: Single missense mutation in the tyrosine kinase catalytic domain of the RET protooncogene is associated with multiple endocrine neoplasia type 2B. Proc Natl Acad Sci USA. 91:1579–1583. 1994.PubMed/NCBI View Article : Google Scholar
5	Hofstra RM, Landsvater RM, Ceccherini I, Stulp RP, Stelwagen T, Luo Y, Pasini B, Höppener JW, van Amstel HK, Romeo G, et al: A mutation in the RET proto-oncogene associated with multiple endocrine neoplasia type 2B and sporadic medullary thyroid carcinoma. Nature. 367:375–376. 1994.PubMed/NCBI View Article : Google Scholar
6	Mulligan LM: 65 years of the double helix: Exploiting insights on the RET receptor for personalized cancer medicine. Endocr Relat Cancer. 25:T189–T200. 2018.PubMed/NCBI View Article : Google Scholar
7	Eng C, Mulligan LM, Smith DP, Healey CS, Frilling A, Raue F, Neumann HP, Pfragner R, Behmel A, Lorenzo MJ, et al: Mutation of the RET protooncogene in sporadic medullary thyroid carcinoma. Genes Chromosom Cancer. 12:209–212. 1995.PubMed/NCBI View Article : Google Scholar
8	Wells SA Jr, Asa SL, Dralle H, Elisei R, Evans DB, Gagel RF, Lee N, Machens A, Moley JF, Pacini F, et al: Revised American thyroid association guidelines for the management of medullary thyroid carcinoma. Thyroid. 25:567–610. 2015.PubMed/NCBI View Article : Google Scholar
9	Waguespack SG, Rich TA, Perrier ND, Jimenez C and Cote GJ: Management of medullary thyroid carcinoma and MEN2 syndromes in childhood. Nat Rev Endocrinol. 7:596–607. 2011.PubMed/NCBI View Article : Google Scholar
10	Bentley DR, Balasubramanian S, Swerdlow HP, Smith GP, Milton J, Brown CG, Hall KP, Evers DJ, Barnes CL, Bignell HR, et al: Accurate whole human genome sequencing using reversible terminator chemistry. Nature. 456:53–59. 2008.PubMed/NCBI View Article : Google Scholar
11	Williams ED: Histogenesis of medullary carcinoma of the thyroid. J Clin Pathol. 19:114–118. 1966.PubMed/NCBI View Article : Google Scholar
12	Takahashi M, Ritz J and Cooper GM: Activation of a novel human transforming gene, ret, by DNA rearrangement. Cell. 42:581–588. 1985.PubMed/NCBI View Article : Google Scholar
13	Uchino S: Prognostic factors for medullary thyroid cancer. J JAES JSTS. 36:158–164. 2019.