Chromosome 18q is lost a high proportion of colorectal and pancreatic cancers. Three candidate tumor suppressor genes, DCC, Smad4 and Smad2 have been identi®ed in this chromosome region. DCC and Smad4 aberrations have been previously identi®ed in pancreatic and colorectal tumors. The aim of this study was to compare the presence of concurrent genetic aberrations in DCC and neighboring Smad4 and Smad2 genes during colorectal and pancreatic distal dissemination. We have used a panel of orthotopically implanted colorectal and pancreatic xenografts and corresponding metastases. We have shown that while LOH at DCC locus occurred at a similar frequency in both tumors, diminished DCC protein expression was exclusively present in colorectal tumors harboring intragenic DCC LOH. In contrast, in pancreatic xenografts loss of DCC protein and mRNA expression was restricted to metastases. Smad4 gene aberrations were detected at a similar frequency in both tumors and were selected for during distal dissemination. Acquisition of alterations in both genes occurred independently. Our results suggest that both DCC and Smad4 contribute to pancreatic and colorectal distal dissemination. However, the role of DCC may dier between both tumor types. Oncogene (2000) 19, 546 ± 555.

Analysis of data suggests that the bacteria surrounding exposed dental implants form a diverse microbiome regardless of the periodontal profile of patients. Further research is needed to clarify the role of these microorganisms in the oral environment.

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severe pulmonary and intestinal disease including ileus at birth and liver cirrhosis at the age 5 years, whereas the other one developed much better with only mild pulmonary changes. Clinical follow-up evaluation of our patient, a 5-year-old girl, was evocative of an intermediary status. Diagnosis of CF was established from positive sweat test at the age of 21 months. At the present time, she shows pulmonary disease and pancreatic insufficiency but not liver disease and develops well under therapy. REFERENCESDeufel A, Deufel T, Golla A, Achatz H, Bertele-Harms R, Roscher AA, Meitinger T (1994) Three novel mutations (1506s S466X, 1651A-T) in exon 10 Zielenski], Rozmahel R, Boron D, Kerem B, Gnelczak Z, Riordan JR, Rommens], Tsui L (1991) Genomic. DNA sequence of the Cystic Fibrosis Transmembrane of the Cystic Fibrosis Transmembrane Conductance regulator (CFTR) detected in patients of southern german descent. Hum Mutat 3:64-66.In 1994, a gene for hereditary breast and ovarian cancer (BRCAI) was isolated by positional cloning (Miki et al., 1994). Mutations in BRCAI are thought to be responsible for more than 80% of inherited breast and ovarian cancer (Easton et al., 1993). Women who harbour BRCAl germline mutations are estimated to have a 85-90% lifetime risk of breast cancer and an elevated risk of ovarian cancer.From the Max-Delbriick-Center (Berlin) collection of families with hereditary breast cancer (Easton et al., 1993) several families were selected for intensive investigation. Genomic DNA was prepared from blood samples and polymerase chain reaction (PCR)-amplified, using the primer pairs indicated by Friedman et al. (1994). The following SSCP analysis (Grade et al., 1994) revealed an aberrant banding pattern in exon 12 of the BRCAl gene in one family that could not be seen in other breast cancer families. Direct sequencing in both directions (sense and antisense strand) of the exon 12 PCR-amplified fragments was performed after alkali strand denaturation and separation of biotinylated primers with streptavidin-coated magnetic beads (Dynal, Oslo, Norway) using the Sequenase Terminator Single-Stranded DNA Sequencing Kit (Applied Biosystems, La Jolla, CA). A heterozygous two base pair (2-bp) deletion was identified in position 4282-4283 (reviewed, but not shown). This deletion leads to the creation of a TGA stop at codon 1389 and a predicted truncation of the BRCAl protein. 4282delAG could not be detected in the BRCA1 gene of 50 unrelated and unaffected individuals.One allele of the BRCAl gene is deleted in three members of the family. Familial history showed that mammary carcinomas occurred at an age of 35, 32, and 33, respectively. One patient suffered on ovarian cancer at an age of 56. This family is a clear example of an early-onset breast-ovarian cancer syndrome. ACKNOWLEDGMENTSWe thank I. Siimnich and H. Zeidler for technical assistance. This work was supported in part by MEC grant RRK13. REFERENCESEaston DF, Bishop T, Ford D, Crockford & the Breast Cancer Linkage Consortium (1993) Genetic linkage analy...