Microsatellite instability differences between familial and sporadic ovarian cancers.
DNA instability, reflected in altered patterns of short tandem repeat sequences (microsatellites) in dividing cells, has been described in hereditary non-polyposis colon cancer (HNPCC) and in other tumor types. Ovarian cancer (OC), although most often a sporadic cancer, can recur, with HNPCC, as part of the Lynch cancer family syndrome. In an investigation of microsatellite instability (MIN) in 90 OC cases, we found MIN in 3/28 (11%) OC cases with, and 8/62 (13%) without, a family history of cancer. For 2/3 MIN+ OC cases with family cancer history consistent with the Lynch cancer family syndrome, we found additional bands in the microsatellite patterns in tumor versus normal tissue (HNPCC-type of MIN), but no germline mutations in two DNA mismatch repair genes, hMSH2 and hMLH1. In 7/8 MIN+ sporadic OC cases distinct MIN patterns not commonly reported in HNPCC were found. These are characterized by partial or total band shifting, leading to fewer bands and/or changes in the intensity of individual bands restricted to the tumor. In only one case was a germline change in hMSH2 or hMLH1 identified: this was subsequently found to be a polymorphism. An apparent hMLH1 somatic change confined to the tumor was found in another case. The fact that we found no germline pathologic mutations in hMSH2 and hMLH1 (predominant sites of mutation in HNPCC) in MIN+ OC cases, suggests that the genetic basis of MIN in OC can be different from that in HNPCC; our finding that distinct microsatellite banding patterns largely distinguish sporadic from familial OC, may reflect the involvement of different DNA repair genes in MIN in individual OC cases.
Arzimanoglou
I I
II
Strang Cancer Prevention Center and Cornell University Medical College, Division of Human Genetics, New York 10021, USA.
Lallas
T
T
Osborne
M
M
Barber
H
H
Gilbert
F
F
D000328:Adult; D000367:Age Factors; D000368:Aged; D001483:Base Sequence; D002352:Carrier Proteins; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics; D017931:DNA Primers; D004268:DNA-Binding Proteins; D005091:Exons; D050556:Fatty Acid-Binding Proteins; D005260:Female; D005819:Genetic Markers; D014644:Genetic Variation; D006801:Humans; D007438:Introns; D018895:Microsatellite Repeats; D008875:Middle Aged; D008969:Molecular Sequence Data; D051718:MutS Homolog 2 Protein; D009363:Neoplasm Proteins / Q000235:genetics; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011518:Proto-Oncogene Proteins / Q000235:genetics
D002352:Carrier Proteins; D017931:DNA Primers; D004268:DNA-Binding Proteins; D050556:Fatty Acid-Binding Proteins; D005819:Genetic Markers; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; C497172:MSH2 protein, human; D051718:MutS Homolog 2 Protein