Sex chromosome alterations associate with tumor progression in sporadic colorectal carcinomas.
OBJECTIVE
The X and Y chromosomes have been associated with malignancy in different types of human tumors. This study attempts to determine the involvement of X chromosome and pseudoautosomal regions (PAR) in sporadic colorectal carcinogenesis.


METHODS
An allelotyping of X chromosome in 20 premalignant and 22 malignant sporadic colorectal tumors (CRC) from female patients and an analysis of losses [loss of heterozygosity (LOH)] on PARs from 44 CRCs and 12 adenomas of male patients were carried out. In male tumors, a fluorescence in situ hybridization analysis was done to identify which sex chromosome was possibly lost.


RESULTS
The LOH frequency in female CRCs was 46% with higher incidence in patients with tumor recurrence than in those who were disease-free (P < 0.01) and with a significant difference from adenomas (11%; P < 0.0001). The LOH rate of PARs in male CRCs was 37% with a frequency significantly higher in patients with recurrence (P < 0.03). These results were maintained also when data from PARs of all 66 male and female patients were cumulated (P < 0.05). LOH in PARs was significantly correlated with LOH at 5q (P < 0.01) and 18q (P < 0.01), early and late events, respectively, in colorectal carcinogenesis. Fluorescence in situ hybridization analysis in male patients with extensive PAR LOH revealed a preferential loss of the Y chromosome.


CONCLUSIONS
Our data suggest a role for sex chromosome deletions in the malignant progression of sporadic CRCs and support the presence in the PARs of putative tumor suppressor genes involved in the progression of human sporadic CRCs.
Department of Pathology and Laboratory Medicine, Medical School, Parma University, Parma, Italy.
Lorena
L
Bottarelli
Cinzia
C
Azzoni
Francesca
F
Necchi
Costanza
C
Lagrasta
Elisa
E
Tamburini
Tiziana
T
D'Adda
Silvia
S
Pizzi
Leopoldo
L
Sarli
Guido
G
Rindi
Cesare
C
Bordi
D000230:Adenocarcinoma / Q000235:genetics*; D000368:Aged; D000369:Aged, 80 and over; D002471:Cell Transformation, Neoplastic; D002869:Chromosome Aberrations; D002874:Chromosome Mapping; D041321:Chromosomes, Human, X / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics; D018450:Disease Progression; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D009693:Nucleic Acid Hybridization; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
D004273:DNA, Neoplasm; D016159:Tumor Suppressor Protein p53