Allelic Loss on Chromosome 9q Is Associated with Lymph Node Metastasis of Primary Breast Cancer

Abstract

Frequent allelic losses on chromosome 9 are seen in a wide variety of human tumors; moreover, two genes (P16 and PTC) whose mutant alleles confer predispositions to some inherited cancer syndromes have been identified on this chromosome. Using 15 highly polymorphic microsatellite markers distributed on both arms of chromosome 9, we tested 96 primary breast carcinomas for allelic loss in order to define the locations of genes that might be involved in this type of tumor. Allelic loss was observed in 37 of the tumors (39%) and detailed deletion mapping identified target regions at 9p21, 9q22.3 and 9q33. Losses at 9q22.3 and 9q33 were correlated with the presence of lymph node metastasis, and allelic loss at 9q22.3 was observed more frequently in scirrhous tumors than in less aggressive histologic types. Therefore, inactivation of tumor suppressor genes in 9q22.3 and 9q33 regions might play a role in progression of breast cancers, especially in metastasis to lymph nodes and in development of scirrhous tumors.

Comparative Genomic Hybridization of Microdissected Familial Ovarian Carcinoma: Two Deleted Regions on Chromosome 15q Not Previously Identified in Sporadic Ovarian Carcinoma

“…A final region of interest is 9q31-33 that showed loss in 16 of 36 (44%) familial ovarian cancer cases. Loss of 9q has been seen in unselected ovarian cancer (Table 2) and harbors a region that is commonly associated with bladder and renal cell carcinoma (Habuchi et al, 1997;Simoneau et al, 1996), although loss of heterozygosity (LOH) of this region has also been linked to metastatic breast cancer (Minobe et al, 1998;Nishizaki et al, 1997). Our analyses suggest that losses at 17p12-13, Xp22, 18q21, 13q14, and 9q31-33 in ovarian cancer are unrelated to hereditary predisposition.…”

Progressive Loss of Syk and Abnormal Proliferation in Breast Cancer Cells

“…In ϳ30% of invasive breast cancer, loss of Syk in cell lines and primary breast tumors can be explained by hypermethylation of the Syk gene (3). Finally, a role for Syk in breast tumorigenesis is suggested by the link of allelic loss of the human Syk locus on chromosome 9q22 to lymph node metastasis of primary breast cancer (13) and by the development of mammary epithelial hyperplasia in mice where the negative Syk regulator c-Cbl was knocked out (14).…”

Syk Interacts with and Phosphorylates Nucleolin To Stabilize Bcl-xL mRNA and Promote Cell Survival

“…It is clear, however, that Syk is not essential for the survival of all cancer cells. In fact, Syk is frequently absent from certain tumor types, such as highly metastatic breast cancer, hepatocellular carcinoma, and melanoma, as a result of gene silencing by promoter methylation (30,(42)(43)(44)(45)(46)(47)(48). The exogenous expression of Syk in such cells decreases cellular motility, invasion, and metastasis (but does not induce apoptosis [30]).…”