Multiple leiomyomas of the esophagus, lung, and uterus in multiple endocrine neoplasia type 1

Jeffrey L. McKeeby, Xiaoming Li, Zhengping Zhuang, Alexander Vortmeyer, Steve Huang, Mark Pirner, Monica C. Skarulis, Laura James-Newton, Stephen J. Marx, Irina A. Lubensky

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant hereditary disorder characterized by multiple parathyroid, pancreatic, duodenal, and pituitary neuroendocrine tumors. Nonendocrine mesenchymal tumors, such as lipomas, collagenomas, and angiofibromas have also been reported. MEN1-associated neuroendocrine and some mesenchymal tumors have documented MEN1 gene alterations on chromosome 11q13. To test whether the MEN1 gene is involved in the pathogenesis of multiple smooth muscle tumors, we examined the 11q13 loss of heterozygosity (LOH) and clonality patterns in 15 leiomyomata of the esophagus, lung, and uterus from five patients with MEN1. Forty sporadic uterine leiomyomata were also studied for 11q13 LOH. LOH analysis was performed using four polymorphic DNA markers at the MEN1 gene locus; D11S480, PYGM, D11S449, and INT-2. 11q13 LOH was detected in 10 of 12 (83%) MEN1-associated esophageal and uterine smooth muscle tumors. In contrast, LOH at the MEN1 gene locus was demonstrated only in 2 of 40 (5%) sporadic uterine tumors. LOH at 11q13 was not documented in three lung smooth muscle tumors from a single patient with MEN1. Ten tumors from two female patients were additionally assessed for clonality by X-chromosome inactivation analysis. The results demonstrated different clonality patterns in multiple tumors in the same organ in each individual patient. The data indicate that leiomyomata of the esophagus and uterus in MEN1 patients arise as independent clones, develop through MEN1 gene alterations, and are an integral part of MEN1. However, the MEN1 gene is not a significant contributor to the tumorigenesis of sporadic uterine leiomyomata.

Original languageEnglish (US)
Pages (from-to)1121-1127
Number of pages7
JournalAmerican Journal of Pathology
Volume159
Issue number3
DOIs
StatePublished - Jan 1 2001
Externally publishedYes

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Multiple Endocrine Neoplasia Type 1
Leiomyoma
Esophagus
Uterus
Lung
Loss of Heterozygosity
Smooth Muscle Tumor
Genes
Neoplasms
Angiofibroma
X Chromosome Inactivation
Neuroendocrine Tumors
Myometrium
Lipoma
Pituitary Neoplasms
Genetic Markers

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Multiple leiomyomas of the esophagus, lung, and uterus in multiple endocrine neoplasia type 1. / McKeeby, Jeffrey L.; Li, Xiaoming; Zhuang, Zhengping; Vortmeyer, Alexander; Huang, Steve; Pirner, Mark; Skarulis, Monica C.; James-Newton, Laura; Marx, Stephen J.; Lubensky, Irina A.

In: American Journal of Pathology, Vol. 159, No. 3, 01.01.2001, p. 1121-1127.

Research output: Contribution to journalArticle

McKeeby, JL, Li, X, Zhuang, Z, Vortmeyer, A, Huang, S, Pirner, M, Skarulis, MC, James-Newton, L, Marx, SJ & Lubensky, IA 2001, 'Multiple leiomyomas of the esophagus, lung, and uterus in multiple endocrine neoplasia type 1', American Journal of Pathology, vol. 159, no. 3, pp. 1121-1127. https://doi.org/10.1016/S0002-9440(10)61788-9
McKeeby, Jeffrey L. ; Li, Xiaoming ; Zhuang, Zhengping ; Vortmeyer, Alexander ; Huang, Steve ; Pirner, Mark ; Skarulis, Monica C. ; James-Newton, Laura ; Marx, Stephen J. ; Lubensky, Irina A. / Multiple leiomyomas of the esophagus, lung, and uterus in multiple endocrine neoplasia type 1. In: American Journal of Pathology. 2001 ; Vol. 159, No. 3. pp. 1121-1127.
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abstract = "Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant hereditary disorder characterized by multiple parathyroid, pancreatic, duodenal, and pituitary neuroendocrine tumors. Nonendocrine mesenchymal tumors, such as lipomas, collagenomas, and angiofibromas have also been reported. MEN1-associated neuroendocrine and some mesenchymal tumors have documented MEN1 gene alterations on chromosome 11q13. To test whether the MEN1 gene is involved in the pathogenesis of multiple smooth muscle tumors, we examined the 11q13 loss of heterozygosity (LOH) and clonality patterns in 15 leiomyomata of the esophagus, lung, and uterus from five patients with MEN1. Forty sporadic uterine leiomyomata were also studied for 11q13 LOH. LOH analysis was performed using four polymorphic DNA markers at the MEN1 gene locus; D11S480, PYGM, D11S449, and INT-2. 11q13 LOH was detected in 10 of 12 (83{\%}) MEN1-associated esophageal and uterine smooth muscle tumors. In contrast, LOH at the MEN1 gene locus was demonstrated only in 2 of 40 (5{\%}) sporadic uterine tumors. LOH at 11q13 was not documented in three lung smooth muscle tumors from a single patient with MEN1. Ten tumors from two female patients were additionally assessed for clonality by X-chromosome inactivation analysis. The results demonstrated different clonality patterns in multiple tumors in the same organ in each individual patient. The data indicate that leiomyomata of the esophagus and uterus in MEN1 patients arise as independent clones, develop through MEN1 gene alterations, and are an integral part of MEN1. However, the MEN1 gene is not a significant contributor to the tumorigenesis of sporadic uterine leiomyomata.",
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AU - Pirner, Mark

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