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Minerva Biotecnologica 1999 March;11(1):7-16

Copyright © 1999 EDIZIONI MINERVA MEDICA

language: English

Genetic predisposition to breast and ovarian cancer. An update on the BRCA1 and BRCA2 genes

Santarosa M., Viel A., Boiocchi M.

Division of Experimantal Oncology 1, Centro di Riferimento Oncologico, Aviano, Italy


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Approximately 5-10% of all ­breast and ovar­ian can­cers are diag­nosed in ­patients ­that ­present oth­er ­breast and/or ovar­ian can­cer cas­es in ­their fam­i­ly, sug­gest­ing an inher­it­able pre­dis­po­si­tion to can­cer. The major­ity of ­these inher­it­able ­forms of ­breast and ovar­ian can­cers are due to alter­a­tions of the two ­tumor sup­pres­sor ­genes recent­ly ­cloned, ­BRCA1 and ­BRCA2. ­BRCA1, local­ized to chro­mo­some 17q21 by genet­ic link­age of ear­ly ­onset ­breast can­cer fam­i­lies, was ­cloned in 1994, and ­BRCA2, map­ping to 13q12-13, was iden­ti­fied in 1995. Although the sup­pres­sive ­effect of ­BRCA1 and ­BRCA2 ­genes is ­still far to be com­plete­ly under­stood, ­much ­progress has ­been ­made to elu­ci­date ­their pos­sible bio­log­i­cal ­roles, and ­many ­efforts ­have ­been ­made to esti­mate the inci­dence and pen­e­trance of ­their muta­tions. In the ­present ­review, the struc­tu­ral com­plex­ity of ­these ­genes and ­their bio­log­i­cal prop­er­ties ­will be dis­cussed, by report­ing ­data ­from the stud­ies on the con­served ­motifs ­among spe­cies and on the inter­act­ing pro­teins. In par­tic­u­lar, the muta­tion­al screen­ing strat­e­gies in use in our labor­a­to­ry as ­well as ­those ­used by oth­er inves­ti­ga­tors ­will be ­described.

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