Microsatellite instability in human solid tumors

• Published in: Cancer Vol. 82; no. 10; pp. 1808 - 1820
• Main Authors: Arzimanoglou, Iordanis I., Gilbert, Fred, Barber, Hugh R. K.
• Format: Journal Article
• Language: English
• Published: New York John Wiley & Sons, Inc 15.05.1998; Wiley-Liss
• Subjects: Biological and medical sciences; Chromosome Mapping; Genome, Human; genomic; human solid tumors; Humans; instability; Medical sciences; microsatellite; Microsatellite Repeats; molecular diagnosis/prognosis; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Mutation; Neoplasms - genetics; Neoplasms - pathology; Prognosis; Tumors; Human; Prognosis; Microsatellite DNA; Histological type; Genetics; Instability; Diagnosis; Mutation; Malignant tumor
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/(SICI)1097-0142(19980515)82:10<1808::AID-CNCR2>3.0.CO;2-J

BACKGROUND Microsatellite instability (MIN) has been identified in a wide variety of human tumors, both familial and sporadic. In this study the authors attempted to correlate MIN with other biologic parameters to assess the significance of MIN in cancer. METHODS The current literature up to May 1997 was reviewed critically. Comparative assessment and analysis of published MIN data in human solid tumors was addressed. RESULTS Based on review of the current medical literature, the following conclusions can be drawn: 1) MIN associated with inherited mutations of the DNA mismatch repair genes (predominantly hMSH2/hMLH1) appears to characterize only the hereditary nonpolyposis colon carcinoma (HNPCC)/Muir‐Torre family cancer syndrome category, and a subset of young colorectal carcinoma patients. Constitutional hMSH2/hMLH1 mutations rarely are reported in other than colon MIN+ tumor types; 2) MIN in non‐HNPCC tumors generally is not associated with somatic mutations in the mismatch DNA repair genes most commonly involved in HNPCC; 3) loci of individual chromosomes containing microsatellite markers demonstrating high MIN frequency may be linked to particular tumor types (tumor specific MIN hot spots); 4) the gel banding patterns of MIN observed in noncolon tumors differ significantly from those reported previously in HNPCC; 5) although overall no association between MIN and histopathology is observed in the literature, a statistically higher MIN frequency has been noted in certain tumor subtypes; and 6) MIN in tumors can be associated with early or late stages of tumor progression, and also has been found in nontumor tissues. CONCLUSIONS Molecular diagnosis using MIN analysis has been documented in at least two types of tumors (HNPCC and sporadic bladder carcinoma), suggesting a potential role of MIN in the diagnosis and/or prognosis of other solid human tumors as well. Cancer 1998;82:1808‐20. © 1998 American Cancer Society. The origin of microsatellite instability (MIN or RER) has been documented in some familial cancer syndromes and early onset sporadic colorectal carcinoma. MIN can be used for molecular diagnosis in two types of tumors (hereditary nonpolyposis colorectal carcinoma and bladder carcinoma), but for the majority of solid tumors further study is needed to assess the significance of MIN.