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Alterations of the fragile histidine triad gene, FHIT, and its encoded products contribute to testicular germ cell tumorigenesis

Kraggerud, SM; Åman, Pierre LU ; Holm, R; Stenwig, AE; Fossa, SD; Nesland, JM and Lothe, RA (2002) In Cancer Research 62(2). p.512-517
Abstract
The fragile histidine triad (FHIT) gene, located within chromosome arm 3p, is a potential target for testicular tumorigenesis. In the present study, 62 primary testicular germ cell tumors were analyzed for allelic imbalance (AI) at 10 loci mapping to chromosome bands 3p14.1-21.1. Twenty-seven tumors (44%) showed AI at one or more 3p loci. The chromosome 3 copy number was evaluated by fluorescence in situ hybridization with centromere and p-telomere probes onto interphase nuclei from 22 of the tumors. Sixteen of these (73%) presented three or more signals of each probe in at least one-third of the nuclei. The combined fluorescence in situ hybridization and AI results indicated that tumors with AI at all loci, in most cases (five of six),... (More)
The fragile histidine triad (FHIT) gene, located within chromosome arm 3p, is a potential target for testicular tumorigenesis. In the present study, 62 primary testicular germ cell tumors were analyzed for allelic imbalance (AI) at 10 loci mapping to chromosome bands 3p14.1-21.1. Twenty-seven tumors (44%) showed AI at one or more 3p loci. The chromosome 3 copy number was evaluated by fluorescence in situ hybridization with centromere and p-telomere probes onto interphase nuclei from 22 of the tumors. Sixteen of these (73%) presented three or more signals of each probe in at least one-third of the nuclei. The combined fluorescence in situ hybridization and AI results indicated that tumors with AI at all loci, in most cases (five of six), reflected an increased chromosome copy number, whereas tumors presenting AI only at some loci reflected interstitial chromosomal changes. A smallest region of overlapping changes could be delineated from tumors showing interstitial chromosomal changes (n = 16). The smallest region of overlapping changes was flanked by D3S1312 and D3S1234 and included parts of FHIT. In the second part of this study, expression analyses of FHIT were performed. Transcripts of aberrant lengths were found in 7 of 17 (41%) analyzed tumors and were identified by sequencing as splice variants. Three different types of transcripts were found, and all lacked exon 3. Immunohistochemical staining showed reduced Fhit protein expression, compared with normal testicular tissue, in 62% (40 of 65) of the testicular germ cell tumors. Although we found a significant association between FHIT mRNA alterations and AI (P = 0.006), altered protein expression did not correlate with AI. The nonepithelial components of teratomas showed strong association with reduced Fhit protein compared with the epithelial component (P < 0.001). Interestingly, reduced Fhit expression seems to be associated with metastasis in the patient at the time of diagnosis, although the association was not statistically significant. (Less)
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author
organization
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type
Contribution to journal
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published
subject
in
Cancer Research
volume
62
issue
2
pages
512 - 517
publisher
American Association for Cancer Research Inc.
external identifiers
  • wos:000173488700031
  • pmid:11809703
  • scopus:0037081094
ISSN
1538-7445
language
English
LU publication?
yes
id
2bd731f2-e38e-4156-8b81-f4826efdbc69 (old id 344221)
alternative location
http://cancerres.aacrjournals.org/cgi/content/abstract/62/2/512
date added to LUP
2007-11-02 11:37:45
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2017-01-01 07:01:55
@article{2bd731f2-e38e-4156-8b81-f4826efdbc69,
  abstract     = {The fragile histidine triad (FHIT) gene, located within chromosome arm 3p, is a potential target for testicular tumorigenesis. In the present study, 62 primary testicular germ cell tumors were analyzed for allelic imbalance (AI) at 10 loci mapping to chromosome bands 3p14.1-21.1. Twenty-seven tumors (44%) showed AI at one or more 3p loci. The chromosome 3 copy number was evaluated by fluorescence in situ hybridization with centromere and p-telomere probes onto interphase nuclei from 22 of the tumors. Sixteen of these (73%) presented three or more signals of each probe in at least one-third of the nuclei. The combined fluorescence in situ hybridization and AI results indicated that tumors with AI at all loci, in most cases (five of six), reflected an increased chromosome copy number, whereas tumors presenting AI only at some loci reflected interstitial chromosomal changes. A smallest region of overlapping changes could be delineated from tumors showing interstitial chromosomal changes (n = 16). The smallest region of overlapping changes was flanked by D3S1312 and D3S1234 and included parts of FHIT. In the second part of this study, expression analyses of FHIT were performed. Transcripts of aberrant lengths were found in 7 of 17 (41%) analyzed tumors and were identified by sequencing as splice variants. Three different types of transcripts were found, and all lacked exon 3. Immunohistochemical staining showed reduced Fhit protein expression, compared with normal testicular tissue, in 62% (40 of 65) of the testicular germ cell tumors. Although we found a significant association between FHIT mRNA alterations and AI (P = 0.006), altered protein expression did not correlate with AI. The nonepithelial components of teratomas showed strong association with reduced Fhit protein compared with the epithelial component (P &lt; 0.001). Interestingly, reduced Fhit expression seems to be associated with metastasis in the patient at the time of diagnosis, although the association was not statistically significant.},
  author       = {Kraggerud, SM and Åman, Pierre and Holm, R and Stenwig, AE and Fossa, SD and Nesland, JM and Lothe, RA},
  issn         = {1538-7445},
  language     = {eng},
  number       = {2},
  pages        = {512--517},
  publisher    = {American Association for Cancer Research Inc.},
  series       = {Cancer Research},
  title        = {Alterations of the fragile histidine triad gene, FHIT, and its encoded products contribute to testicular germ cell tumorigenesis},
  volume       = {62},
  year         = {2002},
}