Nearly identical haploid karyotype in two tumors, masked by the larger pseudo-diploid subclone. D.L. Van Dyke¹, S. Wei², K.G. Monaghan², P. Blunden³, P. Mazzara³, R. Raghavan⁴, A.M. Oliveira¹, A.E. Wiktor¹, G. Keeney¹, R.P. Ketterling¹. 1) Mayo Clinic, Rochester, MN; 2) Henry Ford Hospital, Detroit, MI; 3) St John Medical Center, Detroit, MI; 4) Loma Linda University Medical Center, CA.
   Near-haploid karyotypes in cancer are very uncommon, except in acute lymphoblastic leukemia. They are observed sporadically in sarcoma and carcinoma, but are recurrent findings in inflammatory leiomyosarcoma. We describe the karyotype and genotype of two distinct tumors with strikingly similar nearly identical near-haploid karyotypes - a peritoneal mesothelioma and a retroperitoneal malignant peripheral nerve sheath tumor. The findings suggest that they share some of the same mechanisms of clonal evolution despite their distinct biology. Tumor diagnoses were confirmed by histopathology and immunohistochemistry. Cell cultures were established from tumor adjacent to the ovary (Case 1) or pelvic mass (Case 2). The karyotype of Case 1 (biphasic mesothelioma) was 27,XX,i(5)(p10),+7,der(15)t(8;15)(q24.1;p11.2),+dic(1;20)(p13;p13)[2]/54,idemx2[90]/101-108,idemx4[19]. The chromosome result of Case 2 (malignant peripheral nerve sheath tumor) was 26,X,+i(5)(p10),+7,der(15)t(1;15)(q12;p12),+20[5]/52,idemx2[20]. In both cases, reverse transcriptase polymerase chain reaction analyses were negative for the synovial sarcoma fusion genes. The karyotypes were near-haploid but diploid for 1q, 5p, 7, and 20. Chromosome 7 remains diploid in most near-haploid tumors, suggesting that monosomy or partial loss of chromosome 7 is lethal to these cells. A potential effect of near-haploidy is loss of tumor suppressor gene expression, with the remaining gene inactivated by another mechanism. For mesothelioma, other than p16, p14 and NF2, the importance of tumor suppressor genes is unknown. These cases illustrate an under-appreciated mechanism of global loss of heterozygosity by extensive chromosome loss from a diploid cell population. Near-haploid tumors may be more common than generally recognized because most exhibit a predominant near-diploid subclone masking its near-haploid origin (only two near haploid metaphase cells were found in Case 1).