Whole-exome sequencing of duodenal neuroendocrine tumors in patients with neurofibromatosis type 1

Michaël Noë, Antonio Pea, Claudio Luchini, Matthäus Felsenstein, Stefano Barbi, Feriyl Bhaijee, Raluca Yonescu, Yi Ning, N. Volkan Adsay, Giuseppe Zamboni, Rita T. Lawlor, Aldo Scarpa, G. Johan A. Offerhaus, Lodewijk A.A. Brosens, Ralph H Hruban, Nicholas Roberts, Laura Delong Wood

Research output: Contribution to journalArticle

Abstract

Neurofibromatosis type 1 (NF1) is a hereditary cancer predisposition syndrome characterized by frequent cutaneous and nervous system abnormalities. Patients with NF1 also have an increased prevalence of multiple gastrointestinal and peripancreatic neoplasms—neuroendocrine tumors of the ampulla that express somatostatin are particularly characteristic of NF1. In this study, we characterize the genetic alterations of a clinically well-characterized cohort of six NF1-associated duodenal neuroendocrine tumors using whole-exome sequencing. We identified inactivating somatic mutations in the NF1 gene in three of six tumors; the only other gene altered in more than one tumor was IFNB1. Copy number analysis revealed deletion/loss of heterozygosity of chromosome 22 in three of six patients. Analysis of germline variants revealed germline deleterious NF1 variants in four of six patients, as well as deleterious variants in other tumor suppressor genes in two of four patients with deleterious NF1 variants. Taken together, these data confirm the importance of somatic inactivation of the wild-type NF1 allele in the formation of NF1-associated duodenal neuroendocrine tumors and suggest that loss of chromosome 22 is important in at least a subset of cases. However, we did not identify any genes altered in the majority of NF1-associated duodenal neuroendocrine tumors that uniquely characterize the genomic landscape of this tumor. Still, the genetic alterations in these tumors are distinct from sporadic neuroendocrine tumors occurring at these sites, highlighting that unique genetic alterations drive syndromic tumors.

Original languageEnglish (US)
Pages (from-to)1-7
Number of pages7
JournalModern Pathology
DOIs
StateAccepted/In press - May 30 2018

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Exome
Neurofibromatosis 1
Neuroendocrine Tumors
Chromosomes, Human, Pair 22
Neoplasms
Neurofibromatosis 1 Genes
Hereditary Neoplastic Syndromes
Nervous System Malformations
Loss of Heterozygosity
Somatostatin
Tumor Suppressor Genes
Genes
Alleles

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Whole-exome sequencing of duodenal neuroendocrine tumors in patients with neurofibromatosis type 1. / Noë, Michaël; Pea, Antonio; Luchini, Claudio; Felsenstein, Matthäus; Barbi, Stefano; Bhaijee, Feriyl; Yonescu, Raluca; Ning, Yi; Adsay, N. Volkan; Zamboni, Giuseppe; Lawlor, Rita T.; Scarpa, Aldo; Offerhaus, G. Johan A.; Brosens, Lodewijk A.A.; Hruban, Ralph H; Roberts, Nicholas; Wood, Laura Delong.

In: Modern Pathology, 30.05.2018, p. 1-7.

Research output: Contribution to journalArticle

Noë, M, Pea, A, Luchini, C, Felsenstein, M, Barbi, S, Bhaijee, F, Yonescu, R, Ning, Y, Adsay, NV, Zamboni, G, Lawlor, RT, Scarpa, A, Offerhaus, GJA, Brosens, LAA, Hruban, RH, Roberts, N & Wood, LD 2018, 'Whole-exome sequencing of duodenal neuroendocrine tumors in patients with neurofibromatosis type 1', Modern Pathology, pp. 1-7. https://doi.org/10.1038/s41379-018-0082-y
Noë, Michaël ; Pea, Antonio ; Luchini, Claudio ; Felsenstein, Matthäus ; Barbi, Stefano ; Bhaijee, Feriyl ; Yonescu, Raluca ; Ning, Yi ; Adsay, N. Volkan ; Zamboni, Giuseppe ; Lawlor, Rita T. ; Scarpa, Aldo ; Offerhaus, G. Johan A. ; Brosens, Lodewijk A.A. ; Hruban, Ralph H ; Roberts, Nicholas ; Wood, Laura Delong. / Whole-exome sequencing of duodenal neuroendocrine tumors in patients with neurofibromatosis type 1. In: Modern Pathology. 2018 ; pp. 1-7.
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AU - Pea, Antonio

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AU - Barbi, Stefano

AU - Bhaijee, Feriyl

AU - Yonescu, Raluca

AU - Ning, Yi

AU - Adsay, N. Volkan

AU - Zamboni, Giuseppe

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AU - Scarpa, Aldo

AU - Offerhaus, G. Johan A.

AU - Brosens, Lodewijk A.A.

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AU - Roberts, Nicholas

AU - Wood, Laura Delong

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