CARNEY-COMPLEX, PEUTZ-JEGHERS-SYNDROME, COWDEN-DISEASE, AND BANNAYAN-ZONANA-SYNDROME SHARE CUTANEOUS AND ENDOCRINE MANIFESTATIONS, BUT NOT GENETIC-LOCI

Carney complex (CC), Peutz-Jeghers syndrome (PJS), Cowden disease (CD) , and Bannayan-Zonana syndrome (BZS) share clinical features, such as mucocutaneous lentigines and multiple tumors (thyroid, breast, ovarian , and testicular neoplasms), and autosomal dominant inheritance. A gen etic locus has been identified for CC on chromosome 2 (2p16), and the genes for PJS, CD, and BZS were recently identified; genetic heterogen eity appears likely in both CC and PJS. The genes for PJS and CD/BZS, STK11/LKB1 and PTEN, respectively, may act as tumor suppressors, becau se loss of heterozygosity (LOH) of the PJS and CD/BZS loci has been de monstrated in tumors excised from patients with these disorders. We st udied 2 families with CC in whom the disease could not be shown to seg regate with polymorphic markers from the 2p16 locus. Their members pre sented with lesions frequently seen in PJS and the other lentiginosis syndromes. We also tested 16 tumors and cell lines established from pa tients with CC for LOH involving the PJS and CD/BZS loci. DNA was extr acted from peripheral blood, tumor cell lines, and tissues and subject ed to PCR amplification with primers from microsatellite sequences fla nking the STK11/LKB1 and PTEN genes on 19p13 and 10q23, respectively, and a putative PJS locus on 19q13. All loci were excluded as candidate s in both families with LOD scores less than -2 and/or by haplotype an alysis. LOR for these loci was not present in any of the tumors that w ere histologically identical to those seen in PJS. The overall rate of LOH for the PJS and CD/BZS loci in tumors from patients with CC was l ess than 10%. We conclude that despite substantial clinical overlap am ong CC, PJS, CD, and BZS, LOH for the STK11 and PTEN loci is an infreq uent event in CC-related tumors. Linkage analysis excluded the PJS and CD/BZS loci on chromosomes 19 (19p13 and 19913) and 10 (10q23) from h arboring the gene defect(s) responsible for the phenotype in these 2 f amilies.