Genetic changes in the spectrum of neuroendocrine lung tumors

Naoyoshi Onuki, Ignacio I. Wistuba, William D. Travis, Arvind K. Virmani, Kazuo Yashima, Elizabeth Brambilla, Phillip Hasleton, Adi F. Gazdar

Research output: Contribution to journalArticle

182 Citations (Scopus)

Abstract

BACKGROUND. Recent classifications identify four categories of neuroendocrine (NE) tumors of the lung: low grade typical carcinoid (TC), intermediate grade atypical carcinoid (AC), and high grade large cell neuroendocrine carcinoma (LCNEC) and small cell lung carcinoma (SCLC). METHODS. The authors studied the molecular changes present in 59 archival NE tumors (10 TCs, 11 ACs, 18 LNECs, and 20 SCLCs). Utilizing microdissection and polymerase chain reaction-based assays, the authors examined loss of heterozygosity (LOH) at ten chromosomal regions frequently deleted in lung tumors (3p, 5q, 11q, 13q, and 17p) and for mutations at the p53 and ras genes. RESULTS. With the exception of ras gene mutations, the majority of these changes frequently were present in carcinomas and were present at lower frequencies in carcinoids. LOH at one or more 3p regions was the most frequent change found in the carcinoids. A relatively high incidence of LOH at the MEN1 gene was common in all NE lung tumors. The incidence of LOH and p53 gene abnormalities progressively increased with increasing severity of tumor type. The patterns of p53 gene mutations were different between AC and high grade NE tumors. LOH at 5q21 was correlated with poor survival in the carcinoid group. CONCLUSIONS. Although NE lung tumors have varied etiologies, the results of tHe current study support the clinicopathologic concept that they represent a spectrum ranging from low grade TC to the highly malignant NE carcinomas.

Original languageEnglish (US)
Pages (from-to)600-607
Number of pages8
JournalCancer
Volume85
Issue number3
DOIs
StatePublished - Feb 1 1999

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Neuroendocrine Tumors
Carcinoid Tumor
Loss of Heterozygosity
Lung
p53 Genes
Neuroendocrine Carcinoma
ras Genes
Mutation
Multiple Endocrine Neoplasia Type 1
Large Cell Carcinoma
Microdissection
Incidence
Small Cell Lung Carcinoma
Neoplasms
Carcinoma
Polymerase Chain Reaction
Genes

Keywords

  • Chromosome 3p
  • Chromosome 5q
  • MEN1 gene
  • Neuroendocrine tumors
  • p53 gene
  • Pulmonary carcinoids
  • ras gene
  • Small cell carcinoma of the lung

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Onuki, N., Wistuba, I. I., Travis, W. D., Virmani, A. K., Yashima, K., Brambilla, E., ... Gazdar, A. F. (1999). Genetic changes in the spectrum of neuroendocrine lung tumors. Cancer, 85(3), 600-607. https://doi.org/10.1002/(SICI)1097-0142(19990201)85:3<600::AID-CNCR10>3.0.CO;2-W

Genetic changes in the spectrum of neuroendocrine lung tumors. / Onuki, Naoyoshi; Wistuba, Ignacio I.; Travis, William D.; Virmani, Arvind K.; Yashima, Kazuo; Brambilla, Elizabeth; Hasleton, Phillip; Gazdar, Adi F.

In: Cancer, Vol. 85, No. 3, 01.02.1999, p. 600-607.

Research output: Contribution to journalArticle

Onuki, N, Wistuba, II, Travis, WD, Virmani, AK, Yashima, K, Brambilla, E, Hasleton, P & Gazdar, AF 1999, 'Genetic changes in the spectrum of neuroendocrine lung tumors', Cancer, vol. 85, no. 3, pp. 600-607. https://doi.org/10.1002/(SICI)1097-0142(19990201)85:3<600::AID-CNCR10>3.0.CO;2-W
Onuki N, Wistuba II, Travis WD, Virmani AK, Yashima K, Brambilla E et al. Genetic changes in the spectrum of neuroendocrine lung tumors. Cancer. 1999 Feb 1;85(3):600-607. https://doi.org/10.1002/(SICI)1097-0142(19990201)85:3<600::AID-CNCR10>3.0.CO;2-W
Onuki, Naoyoshi ; Wistuba, Ignacio I. ; Travis, William D. ; Virmani, Arvind K. ; Yashima, Kazuo ; Brambilla, Elizabeth ; Hasleton, Phillip ; Gazdar, Adi F. / Genetic changes in the spectrum of neuroendocrine lung tumors. In: Cancer. 1999 ; Vol. 85, No. 3. pp. 600-607.
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abstract = "BACKGROUND. Recent classifications identify four categories of neuroendocrine (NE) tumors of the lung: low grade typical carcinoid (TC), intermediate grade atypical carcinoid (AC), and high grade large cell neuroendocrine carcinoma (LCNEC) and small cell lung carcinoma (SCLC). METHODS. The authors studied the molecular changes present in 59 archival NE tumors (10 TCs, 11 ACs, 18 LNECs, and 20 SCLCs). Utilizing microdissection and polymerase chain reaction-based assays, the authors examined loss of heterozygosity (LOH) at ten chromosomal regions frequently deleted in lung tumors (3p, 5q, 11q, 13q, and 17p) and for mutations at the p53 and ras genes. RESULTS. With the exception of ras gene mutations, the majority of these changes frequently were present in carcinomas and were present at lower frequencies in carcinoids. LOH at one or more 3p regions was the most frequent change found in the carcinoids. A relatively high incidence of LOH at the MEN1 gene was common in all NE lung tumors. The incidence of LOH and p53 gene abnormalities progressively increased with increasing severity of tumor type. The patterns of p53 gene mutations were different between AC and high grade NE tumors. LOH at 5q21 was correlated with poor survival in the carcinoid group. CONCLUSIONS. Although NE lung tumors have varied etiologies, the results of tHe current study support the clinicopathologic concept that they represent a spectrum ranging from low grade TC to the highly malignant NE carcinomas.",
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T1 - Genetic changes in the spectrum of neuroendocrine lung tumors

AU - Onuki, Naoyoshi

AU - Wistuba, Ignacio I.

AU - Travis, William D.

AU - Virmani, Arvind K.

AU - Yashima, Kazuo

AU - Brambilla, Elizabeth

AU - Hasleton, Phillip

AU - Gazdar, Adi F.

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N2 - BACKGROUND. Recent classifications identify four categories of neuroendocrine (NE) tumors of the lung: low grade typical carcinoid (TC), intermediate grade atypical carcinoid (AC), and high grade large cell neuroendocrine carcinoma (LCNEC) and small cell lung carcinoma (SCLC). METHODS. The authors studied the molecular changes present in 59 archival NE tumors (10 TCs, 11 ACs, 18 LNECs, and 20 SCLCs). Utilizing microdissection and polymerase chain reaction-based assays, the authors examined loss of heterozygosity (LOH) at ten chromosomal regions frequently deleted in lung tumors (3p, 5q, 11q, 13q, and 17p) and for mutations at the p53 and ras genes. RESULTS. With the exception of ras gene mutations, the majority of these changes frequently were present in carcinomas and were present at lower frequencies in carcinoids. LOH at one or more 3p regions was the most frequent change found in the carcinoids. A relatively high incidence of LOH at the MEN1 gene was common in all NE lung tumors. The incidence of LOH and p53 gene abnormalities progressively increased with increasing severity of tumor type. The patterns of p53 gene mutations were different between AC and high grade NE tumors. LOH at 5q21 was correlated with poor survival in the carcinoid group. CONCLUSIONS. Although NE lung tumors have varied etiologies, the results of tHe current study support the clinicopathologic concept that they represent a spectrum ranging from low grade TC to the highly malignant NE carcinomas.

AB - BACKGROUND. Recent classifications identify four categories of neuroendocrine (NE) tumors of the lung: low grade typical carcinoid (TC), intermediate grade atypical carcinoid (AC), and high grade large cell neuroendocrine carcinoma (LCNEC) and small cell lung carcinoma (SCLC). METHODS. The authors studied the molecular changes present in 59 archival NE tumors (10 TCs, 11 ACs, 18 LNECs, and 20 SCLCs). Utilizing microdissection and polymerase chain reaction-based assays, the authors examined loss of heterozygosity (LOH) at ten chromosomal regions frequently deleted in lung tumors (3p, 5q, 11q, 13q, and 17p) and for mutations at the p53 and ras genes. RESULTS. With the exception of ras gene mutations, the majority of these changes frequently were present in carcinomas and were present at lower frequencies in carcinoids. LOH at one or more 3p regions was the most frequent change found in the carcinoids. A relatively high incidence of LOH at the MEN1 gene was common in all NE lung tumors. The incidence of LOH and p53 gene abnormalities progressively increased with increasing severity of tumor type. The patterns of p53 gene mutations were different between AC and high grade NE tumors. LOH at 5q21 was correlated with poor survival in the carcinoid group. CONCLUSIONS. Although NE lung tumors have varied etiologies, the results of tHe current study support the clinicopathologic concept that they represent a spectrum ranging from low grade TC to the highly malignant NE carcinomas.

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KW - Chromosome 5q

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