PMID- 14713256
OWN - NLM
STAT- MEDLINE
DCOM- 20040914
LR  - 20191108
IS  - 1351-0088 (Print)
IS  - 1351-0088 (Linking)
VI  - 10
IP  - 4
DP  - 2003 Dec
TI  - Genetics of neuroendocrine and carcinoid tumours.
PG  - 437-50
AB  - Neuroendocrine tumours (NETs) originate in tissues that contain cells derived 
      from the embryonic neural crest, neuroectoderm and endoderm. Thus, NETs occur at 
      many sites in the body, although the majority occur within the 
      gastro-entero-pancreatic axis and can be subdivided into those of foregut, midgut 
      and hindgut origin. Amongst these, only those of midgut origin are generally 
      argentaffin positive and secrete serotonin, and hence only these should be 
      referred to as carcinoid tumours. NETs may occur as part of complex familial 
      endocrine cancer syndromes, such as multiple endocrine neoplasia type 1 (MEN1), 
      although the majority occur as non-familial (i.e. sporadic) isolated tumours. 
      Molecular genetic studies have revealed that the development of NETs may involve 
      different genes, each of which may be associated with several different 
      abnormalities that include point mutations, gene deletions, DNA methylation, 
      chromosomal losses and chromosomal gains. Indeed, the foregut, midgut and hindgut 
      NETs develop via different molecular pathways. For example, foregut NETs have 
      frequent deletions and mutations of the MEN1 gene, whereas midgut NETs have 
      losses of chromosome 18, 11q and 16q and hindgut NETs express transforming growth 
      factor-alpha and the epidermal growth factor receptor. Furthermore, in lung NETs, 
      a loss of chromosome 3p is the most frequent change and p53 mutations and 
      chromosomal loss of 5q21 are associated with more aggressive tumours and poor 
      survival. In addition, methylation frequencies of retinoic acid receptor-beta, 
      E-cadherin and RAS-associated domain family genes increase with the severity of 
      lung NETs. Thus the development and progression of NETs is associated with 
      specific genetic abnormalities that indicate the likely involvement of different 
      molecular pathways.
FAU - Leotlela, P D
AU  - Leotlela PD
AD  - Nuffield Department of Medicine, University of Oxford, Botnar Research Centre, 
      Nuffield Orthopaedic Centre, Headington, Oxford OX3 7LD, UK.
FAU - Jauch, A
AU  - Jauch A
FAU - Holtgreve-Grez, H
AU  - Holtgreve-Grez H
FAU - Thakker, R V
AU  - Thakker RV
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - England
TA  - Endocr Relat Cancer
JT  - Endocrine-related cancer
JID - 9436481
RN  - 0 (MEN1 protein, human)
RN  - 0 (Proto-Oncogene Proteins)
SB  - IM
MH  - Carcinoid Tumor/*genetics
MH  - Chromosome Aberrations
MH  - DNA Methylation
MH  - Female
MH  - Humans
MH  - Loss of Heterozygosity
MH  - Male
MH  - Neuroendocrine Tumors/*genetics
MH  - Oncogenes
MH  - Pedigree
MH  - Proto-Oncogene Proteins/genetics
RF  - 114
EDAT- 2004/01/10 05:00
MHDA- 2004/09/15 05:00
CRDT- 2004/01/10 05:00
PHST- 2004/01/10 05:00 [pubmed]
PHST- 2004/09/15 05:00 [medline]
PHST- 2004/01/10 05:00 [entrez]
AID - 10.1677/erc.0.0100437 [doi]
PST - ppublish
SO  - Endocr Relat Cancer. 2003 Dec;10(4):437-50. doi: 10.1677/erc.0.0100437.