Intratumoral heterogeneity in microsatellite alterations in BRCA1 and PTEN regions in sporadic colorectal cancer.
BACKGROUND
Chromosome regions 17q21 (BRCA1) and 10q23 (PTEN) have been found deleted in colorectal cancer.


METHODS
We studied the frequency of loss of heterozygosity (LOH) in these 2 regions in 214 patients with only 1 sample per tumor and in 100 patients with several samples per tumor. Three microsatellite markers of each region were used for the LOH test. The polymerase chain reaction product was electrophoresed in 8% polyacrylamide gels, and band intensity was shown by silver staining.


RESULTS
The proportions of LOH in the two regions were 38.4% for 17q21 and 30.8% for 10q23 in the group of 214 and were 47.7% for 17q21 and 34.7% for 10q23 in the group of 100. We found a high correlation between the LOH in both regions (P <.001), where 81% of LOH in 10q23 region was matched by concomitant LOH in 17q21. In the group of tumors with several samples (group of 100), 39% and 68% did not present LOH in the 17q21 and 10q23 regions, respectively, in all of their tumor samples. However, in the 20 patients with LOH in both regions in the group of 100 (several samples per tumor), all samples with LOH in 10q23 also had LOH in 17q21, whereas not all samples with LOH in 17q21 had LOH in 10q23.


CONCLUSIONS
These results show that colorectal cancer is highly heterogeneous, at least for these tumors markers, and suggest a sequential acquisition pattern of these anomalies during tumor growth, in which changes in 17q21 could occur before those in 10q23.
Garcia
Jose M
JM
Department of Medical Oncology, Hospital Universitario Puerta de Hierro, Madrid, Spain.
Rodriguez
Rufo
R
Silva
Javier
J
Muñoz
Concepción
C
Dominguez
Gemma
G
Silva
Jose M
JM
Carcereny
Enric
E
Provencio
Mariano
M
España
Pilar
P
Bonilla
Félix
F
D000368:Aged; D016009:Chi-Square Distribution; D002879:Chromosomes, Human, Pair 10; D002886:Chromosomes, Human, Pair 17; D015179:Colorectal Neoplasms / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D019398:Genes, BRCA1; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats; D051059:PTEN Phosphohydrolase; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics*; D016133:Polymerase Chain Reaction; D025521:Tumor Suppressor Proteins / Q000235:genetics*
D025521:Tumor Suppressor Proteins; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human