ALLELIC LOSS ON CHROMOSOME 1P IS ASSOCIATED WITH PROGRESSION AND LYMPH-NODE METASTASIS OF PRIMARY BREAST-CARCINOMA

BACKGROUND. Frequent allelic losses on the short arm of chromosome 1 h ave been observed in a wide variety of human tumors. Cytogenetic and m olecular genetic studies in breast carcinomas have shown frequent alte rations on chromosome 1, involving loss of 1p or gain of 1q. METHODS. To define the locations of tumor suppressor genes, 143 primary breast carcinomas were examined for allelic loss using 15 highly polymorphic microsatellite markers on 1p. Correlations also were sought between al lelic loss on 1p and several clinicopathologic parameters. RESULTS. Al lelic loss was observed in 73 of the tumors (51%). Detailed deletion m apping identified target regions at 1p36, 1p34-p35, and 1p22-p31. Alle lic losses at 1.36 or 1p34-p35 were observed more frequently in tumors of the solid tubular and scirrhous types than in less aggressive hist ologic types. Conversely, allelic loss at 1p22-p31 was correlated with lymph node metastasis and a tumor size > 2 cm. CONCLUSIONS. Inactivat ion of tumor suppressor genes that lie in either 1p36 or 1p34-p35 migh t affect carcinogenic mechanisms in a histologic type specific manner, especially the solid tubular and scirrhous types. Alterations of one or more tumor suppressor genes at 1p22-p31 may play a role at late sta ges of breast carcinogenesis, especially with regard to local progress ion and lymph node metastasis. (C) 1998 American Cancer Society.