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Originally published as Ann Surg Oncol Early Release 10.1245/ASO.2003.02.004 on September 8, 2003

Annals of Surgical Oncology 10:876-881 (2003)
© 2003 Society of Surgical Oncology
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ORIGINAL ARTICLES

Intratumoral Heterogeneity in Microsatellite Alterations in BRCA1 and PTEN Regions in Sporadic Colorectal Cancer

Jose M. Garcia, MD, Rufo Rodriguez, MD, Javier Silva, PhD, Concepción Muñoz, MD, Gemma Dominguez, PhD, Jose M. Silva, PhD, Enric Carcereny, MD, Mariano Provencio, MD, Pilar España, MD and Félix Bonilla, MD

From the Department of Medical Oncology (JMG, JS, GD, JMS, EC, MP, PE, FB), Hospital Universitario Puerta de Hierro, Madrid, Spain; and Departments of Pathology (RR) and Gastroenterology (CM), Hospital Virgen de la Salud, Toledo, Spain.

Correspondence: Address correspondence and reprint requests to: Felix Bonilla, MD, Department of Medical Oncology, Hospital Universitario Puerta de Hierro, C/San Martin de Porres 4, E-28035 Madrid, Spain; Fax: 34-91-373-7667; E-mail: felixbv{at}stnet.es

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.

Key Words: Colorectal cancer • LOH • BRCA1 • PTEN • Tumor heterogeneity




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