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STR SIZE MUTATION OR LOSS OF HETEROZYGOSITY AT DIFFERENT LOCI CONFOUND ENGRAFTMENT AND TYPING ANALYSIS, A PHENOMENON PREVALENT IN AML.
Shalini E. Pereira Ph.D. 1, Tamara Vayntrub CHS, MT(ASCP) 1, Debra Hiraki Ph.D. 1 and Carl F. Grumet M.D. 1. 1 Stanford Histocompatibility Laboratory, Stanford University, Palo Alto, CA, USA .
Clonal chromosomal abnormalities are often found in the tumor cells of patients with solid tumors and leukemias. Among the abnormalities have been the down-regulation of HLA Class I, postulated to provide tumor cells with an escape mechanism from cytotoxic T lymphocytes and NK cells, and the instability of short tandem repeat (STR) DNA sequences, which has been attributed to defective DNA mismatch repair mechanisms. Because these chromosomal aberrations can affect HLA typing and/or hematopoietic stem cell transplant (HSCT) engraftment analysis, we describe here the abnormalities we have observed during routine testing of 
600 HSCT patients. STR testing was performed by following 1- 4 informative loci from among a panel of 10-16 STR primer sets. HLA molecular testing was performed initially by Reference Strand Conformational Analysis and later by Sequence Based Typing. We observed 7 cases of loss of heterozygosity: 4 in STR markers, 3 in the HLA Class I region and 1 case of an STR length mutation. 7 of the patients suffered from AML and 1 from myelofibrosis. AML/ myelofibrosis patients represent 12% of all HSCT at our center; thus chromosomal abnormalities were encountered in 10% of AML/ myelofibrosis patients tested. The chromosomal abnormality was large enough to be observed in cytogenetic studies in 5 of the cases but no discernable cytogenetic abnormalities were observed in 2 cases; cytogenetic data were not available in the remaining case. These results highlight some of the problems encountered and the possibility for interpretive errors that can arise when analyzing molecular typing and engraftment data, particularly among AML/ myelofibrosis patients.