Interstitial deletions including chromosome 3 common eliminated region 1 (C3CER1) prevail in human solid tumors from 10 different tissues.
A human chromosomal segment regularly lost during tumor formation of microcell hybrids in SCID mice has been mapped to 3p21.3. This segment, called chromosome 3 common eliminated region 1 (C3CER1, also referred to as CER1), may harbor multiple tumor-suppressor genes. Because it was found that similar regions were eliminated in an inter- and intraspecies system and in two tumor types (mouse fibrosarcoma and human renal cell carcinoma), we hypothesized that the importance of C3CER1 would transgress tissue specificity, that is, it could occur in tumors derived from multiple tissues. To evaluate the loss of C3CER1 in various human tumor types, we conducted loss of heterozygosity (LOH) analysis of 576 human solid tumors from 10 different tissues and compared the frequency of deletion in the C3CER1 area to that in two other regions on 3p: the FHIT/FRA3B region, at 3p14.2, and the VHL region, at 3p25.3. Deletions were detected in the C3CER1 region in 83% of informative tumors. Half (47%) the LOH-positive tumors showed LOH at all informative markers, indicating a large deletion. The other half (53%) had a discontinuous LOH pattern, suggesting interstitial deletions or breakpoints. The proportion of tumors with C3CER1 deletions was high in all tumor types investigated, ranging from 70% to 94%, except for the soft-tissue sarcomas (40%). In the VHL and FHIT regions, deletions were observed in 73% and 43%, respectively, of the tumors. Of the three 3p regions analyzed, the highest deletion frequency was observed in the C3CER1 region. Furthermore, we demonstrated that the interstitial deletions including C3CER1 prevail over 3p14.2-pter losses in solid tumors.
Petursdottir
Thorgunnur Eyfjord
TE
Department of Pathology, Landspitali University Hospital, Reykjavik, Iceland.
Thorsteinsdottir
Unnur
U
Jonasson
Jon Gunnlaugur
JG
Moller
Pall Helgi
PH
Huiping
Chen
C
Bjornsson
Johannes
J
Egilsson
Valgardur
V
Imreh
Stefan
S
Ingvarsson
Sigurdur
S
D017766:Acid Anhydride Hydrolases / Q000235:genetics; D014408:Biomarkers, Tumor; D045744:Cell Line, Tumor; D002893:Chromosomes, Human, Pair 3 / Q000648:ultrastructure*; D005260:Female; D017353:Gene Deletion; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D008957:Models, Genetic; D009363:Neoplasm Proteins / Q000235:genetics; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D025521:Tumor Suppressor Proteins / Q000235:genetics; D044767:Ubiquitin-Protein Ligases / Q000235:genetics; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D000099170:Bis(5'-adenosyl)triphosphatase
D017766:Acid Anhydride Hydrolases; D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D000099170:Bis(5'-adenosyl)triphosphatase; C497446:VHL protein, human