Microsatellite repeat instability: Comparison of molecular lesions with tumor karyotype
- Henry Ford Hospital, Detroit, MI (United States); and others
Microsatellite repeat (MR) instability (MRI) (expansion or contraction of one or both alleles) has been observed in hereditary nonpolyposis colon cancer, gastric cancers, non-small cell lung, endometrial, breast and bladder cancers, and occasionally in squamous cell carcinomas in the head and neck region (SCCHN). Of 44 SCCHN studied for loss of heterozygosity (LOH) at MR loci, only HFH-SCC-20 exhibited extensive MRI. Tumor HFH-SCC-20 was a T4N3MO deeply invasive, poorly differentiated SCCHN of the right tonsillar fossa and base of tongue. The tumor karyotypes obtained from early cultures (7 and 10 day harvests) were: 46,XY,del(3)(p11p24),+i(5p),del(11)(q14q25),del(13)(q13),del(14)(q21),der(16)t(16,21)(q11;q21),-21[9]/92,idemx2[3], with net loss of the chromosomal segments 3p11-p24, 11q14-q25, 13q13-qter, 14q21-qter,16q11-qter, and 21pter-q21. The patient`s constitutional karyotype was 46,XY. Tumor and normal lymphocyte DNA from this patient were compared using 20 MRs on 3p, 5q, 8p, 9p, 9q, 18q, and 21q. The results were informative at 19 MR loci: 14 had MR1, two had LOH, and 3 retained heterozygosity. Expansion of one allele was observed at 10 MR loci and of both alleles at the D9S200 locus, D9S199 and D21S11 exhibited expansion of one allele and contraction of the other; and D8S897 exhibited LOH with expansion of the remaining allele. The LOH at the L1B3-15CA locus (at 3p21), and the absence of LOH at loci on 5q, 9p, 18q, and 21q are consistent with the karyotypic interpretation. LOH for the ABL (9q34) and D8S87 (8p22-cen) suggests that a submicroscopic deletion or other genetic change occurred at these loci. The pattern of genomic and cytogenetic alteration in HFH-SCC-20 indicates that (1) MR1 is not associated with visible cytogenetic alterations at the same site, (2) MR1 is the primary mechanism of mutation in some SCCHN tumors, and (3) patterns of MR1 and LOH will provide clues for tumor behavior and evolution.
- OSTI ID:
- 133604
- Report Number(s):
- CONF-941009-; ISSN 0002-9297; TRN: 95:005313-0334
- Journal Information:
- American Journal of Human Genetics, Vol. 55, Issue Suppl.3; Conference: 44. annual meeting of the American Society of Human Genetics, Montreal (Canada), 18-22 Oct 1994; Other Information: PBD: Sep 1994
- Country of Publication:
- United States
- Language:
- English
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