PCR was used to study LOH in 60 breast cancer cases for which PDWA and/or atypical hyperplasia coexisted within the surgical specimen (O’Connell et al., 1994). This study found frequent LOH at 17q21, 16q21, and 2pter in hyperplastic lesions (16-25%). The most valuable information from this study was the finding that LOH patterns were frequently shared among different levels of progression within the same lesion: 50% of hyperplastic lesions shared LOH with coexistent DCIS and 80% of DCIS shared LOH with coexistent invasive cancer. Thus, early proliferative lesions are very likely to be precursors in the progression to breast cancer.
Correlations of different sets of genetic alterations have been described in a number of studies: LOH on chromosomes Up, 17p, and 18q frequently occurred in the same tumor in one study (Callahan et al., 1992); LOH at 1 Ip and 1 Iq were independent of each other, but 90% of tumors with LOH at 1 Iq also showed LOH at 17p in another (Carter et al., 1994); and concordant loss of 17p and 16q and of 13q and 17p as well as loss of 17p with erbB-2 amplification were seen in a third study (Sato et al., 1991). These findings lend credence to the existence of complementation groups in breast cancer development.
Understanding of the genetic basis of the development of proliferative breast disease and progression obviously requires much more work. The use of LOH patterns to determine complementation groups could be very informative in deciphering the role of various gene deletions, amplifications, and deletions and altered transcriptional/translational regulation observed in various studies.
Fred Raymond Miller
Advances in Oncobiology