Expression of unfolded protein response markers in the pheochromocytoma with Waardenburg syndrome: a case report.

Abstract

BACKGROUND:

It is clinically emergent to further understand the pathological mechanism to advance therapeutic strategy for endocrine tumors. A high amount of secretory protein with tumorigenic triggers are thought to induce unfolded protein response in endoplasmic reticulum in endocrine tumors, but its evidence is limited.

CASE PRESENTATION:

A 40-year-old woman had an approximately 10-year history of intermittent headaches. After the incidental detection of a mass in her right adrenal gland by CT scan, she was admitted to our hospital. She had been diagnosed as type 1 Waardenburg syndrome with the symptoms of dystopia canthorum, blue iris, and left sensorineural hearing loss. Urinary catecholamine levels were markedly elevated. 123I-MIBG scintigraphy showed uptake in the mass in her adrenal gland. After the adrenalectomy, her headaches disappeared and urinary catecholamine levels decreased to normal range within 2 weeks. Genome sequencing revealed germline mutation of c.A175T (p.Ile59Phe) in transcription factor PAX3 gene and somatic novel mutation of c.1893_1898del (p. Asp631_Leu633delinsGlu) in proto-oncogene RET in her pheochromocytoma. RNA expression levels of RET were increased 139 times in her pheochromocytoma compared with her normal adrenal gland. Those of unfolded protein response markers, Bip/GRP78, CHOP, ATF4, and ATF6, were also increased in the pheochromocytoma.

CONCLUSION:

We report a rare case of pheochromocytoma with type 1 Waardenburg syndrome. This is the first case to show the activation of unfolded protein response in the pheochromocytoma with the novel somatic mutation in RET gene. Our findings may support that unfolded protein response is activated in endocrine tumors, which potentially could be a candidate of therapeutic target.

• Authors: Shuhei Morita, Ken Takeshima, Hiroyuki Ariyasu, Yasushi Furukawa, Shohei Kishimoto, Tomoya Tsuji, Shinsuke Uraki, Hiroyuki Mishima, Akira Kinoshita, Yuichi Takahashi, Hidefumi Inaba, Hiroshi Iwakura, Hiroto Furuta, Masahiro Nishi, Asako Doi, Shin-Ichi Murata, Koh-Ichiro Yoshiura, Takashi Akamizu
• Journal: BMC endocrine disorders (BMC Endocr Disord) Vol. 20 Issue 1 Pg. 90 (Jun 22 2020) ISSN: 1472-6823 [Electronic] England
• PMID: 32571297 (Publication Type: Case Reports, Journal Article)

Chemical References

• Biomarkers
• Endoplasmic Reticulum Chaperone BiP
• HSPA5 protein, human
• MAS1 protein, human
• Proto-Oncogene Mas
• Proto-Oncogene Proteins c-ret
• RET protein, human

Topics

• Adrenal Gland Neoplasms (complications, metabolism, pathology, surgery)
• Adrenalectomy
• Adult
• Biomarkers (analysis)
• Endoplasmic Reticulum Chaperone BiP
• Female
• Germ-Line Mutation
• Humans
• Pheochromocytoma (complications, metabolism, pathology, surgery)
• Prognosis
• Proto-Oncogene Mas
• Proto-Oncogene Proteins c-ret (genetics)
• Unfolded Protein Response
• Waardenburg Syndrome (complications, metabolism, pathology, surgery)