Genetic alterations on chromosome 16 and 17 are important features of ductal carcinoma in situ of the breast and are associated with histologic type

We analysed the involvement of known and putative tumour suppressor- and on cogene loci in ductal carcinoma in situ (DCIS) by microsatellite analysis ( LOH), Southern blotting and comparative genomic hybridization (CGH). A tota l of 78 pure DCIS cases, classified histologically as well, intermediately and poorly differentiated, were examined for LOH with 76 markers dispersed along all chromosome arms. LOH on chromosome 17 was more frequent in poorly differentiated DCIS (70%) Compared to well-differentiated DCIS (17%), wher eas loss on chromosome 16 was associated with well- and intermediately diff erentiated DCIS (66%). For a subset we have done Southern blot- and CGH ana lysis. C-erbB2/neu was amplified in 30% of poorly differentiated DCIS. No a mplification was found of c-myc, mdm2, bek, flg and the epidermal growth fa ctor (EGF)-receptor, By CGH, most frequent alterations in poorly differenti ated DCIS were gains on 8q and 17q22-24 and deletion on 17p, whereas in wei l-differentiated DCIS amplification on chromosome Iq and deletion on 16q we re found. In conclusion, our data indicates that inactivation of a yet unkn own tumour suppressor gene on chromosome 16q is implicated in the developme nt of most well and intermediately differentiated DCIS whereas amplificatio n and inactivation of various genes on chromosome 17 are implicated in the development of poorly differentiated DCIS. Furthermore these data show that there is a genetic basis for the classification of DCIS in a well and poor ly differentiated type and support the evidence of different genetic routes to develop a specific type of carcinoma in situ of the breast. (C) 1999 Ca ncer Research Campaign.