Loss of heterozygosity on chromosome 4q32-35 in sporadic basal cell carcinomas: evidence for the involvement of p33ING2/ING1L and SAP30 genes.
BACKGROUND
Studies on basal cell carcinoma (BCC) have demonstrated that patched gene and p53 gene located at 9q22.3 and 17p13 are the main genes responsible for the onset of this tumor. In order to identify a possible involvement of other tumor suppressor genes, we screened 19 cases of BCCs for loss of heterozygosity (LOH).


METHODS
The analysis was performed on tumoral tissue and on corresponding normal tissue by using a panel of 37 polymorphic markers spanning 26 chromosomal regions.


RESULTS
We observed that only four chromosomal regions, 4q32 (30.00%), 4q35 (27.27%), 9q21-22 (28.57%), and 9q22-qter (35.71%), demonstrated a significative LOH (>20%), even if others show a borderline percentage (15-20%) of imbalance (1q32, 3p24, 10p22.1, and 17q21.3).


CONCLUSIONS
Our findings suggest that a new chromosomal region mapping in the long arm of chromosome 4 could be involved in sporadic BCC carcinogenesis. Further analyses indicate that the minimal deleted region in 4q32-35 includes p33ING2/ING1L and SAP30, whose deletion could impair the G1-phase checkpoint control and favor gene silencing, respectively.
Sironi
Elena
E
Laboratory of Human Genetics, Dermatologic Clinic, Department of Medicine Surgery and Dental Sciences S. Paolo, University of Milan, Via A. di Rudini 8, 20122 Milan, Italy.
Cerri
Amilcare
A
Tomasini
Dario
D
Sirchia
Silvia Maria
SM
Porta
Giovanni
G
Rossella
Franca
F
Grati
Francesca Romana
FR
Simoni
Giuseppe
G
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002280:Basal Cell Carcinoma / Q000235:genetics* / Q000473:pathology; D002894:Chromosomes, Human, Pair 4; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D006655:Histone Deacetylases / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D018160:Receptors, Cytoplasmic and Nuclear; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology; D025521:Tumor Suppressor Proteins / Q000235:genetics*
D004273:DNA, Neoplasm; D018398:Homeodomain Proteins; C444654:ING2 protein, human; D018160:Receptors, Cytoplasmic and Nuclear; C113294:SAP30 protein, human; D025521:Tumor Suppressor Proteins; D006655:Histone Deacetylases