Yasuhiko Kaneko

15/17 TRANSLOCATION IN ACUTE PROMYELOCYTIC LEUKÆMIA

be deemed acceptably controlled on the basis of the tabulated data? Patients previously thought to be well controlled on cromoglycate may show no change in symptom frequency when the drug is discontinued or placebo substituted, possibly owing to spontaneous improvement in the disease over a long period.3 these problems may be overcome by comparing cromoglycate with placebo immediately before the trial or incorporating a double placebo period into the trial, neither of which was done in this study. Insufficient evidence is available to decide whether theophylline is as effective as cromoglycate in the prophylaxis of asthmatic symptoms in true cromoglycate responders. The conclusion that cromoglycate was effective in the management of asthma seems to be unfounded.

Establishment and characterization of a novel human desmoplastic small round cell tumor cell line, JN-DSRCT-1.

The exact nature of the desmoplastic small round cell tumor (DSRCT) remains controversial. More detailed analyses might be facilitated by the establishment of permanent DSRCT cell lines. To date, however, no human DSRCT cell line has been reported. In this study, we report the establishment of a new human cell line, JN-DSRCT-1, from the pleural effusion of a 7-year-old boy with pulmonary metastasis from a typical intra-abdominal DSRCT. JN-DSRCT-1 cells were small round or spindle shaped with oval nuclei and have been maintained continuously in vitro for over 190 passages during more than 40 months. Histologic features of the heterotransplanted tumors in severe combined immunodeficiency mouse were essentially the same as those of the original DSRCT, revealing nests or clusters of small round cells embedded in an abundant desmoplastic stroma. Both in vitro and in vivo, the cells exhibited immunopositive reactions for vimentin, desmin, cytokeratins (AE1/AE3 and CAM 5.2), epithelial membrane antigen, neuron-specific antigen, and CD57 (Leu-7). JN-DSRCT-1 cells exhibited a pathognomonic t(11;22)(p13;q12) translocation by cytogenetic analysis. In addition, RT-PCR and sequencing analysis revealed a chimeric transcriptional message of the Ewing’s sarcoma gene exon 10 fused to the Wilms’ tumor gene exon 8. To our knowledge, this is the first permanent human DSRCT cell line. The JN-DSRCT-1 cell line, which exhibits the unique morphologic and genetic characteristics of DSRCT, will be extremely useful for a variety of important studies such as the pathogenic mechanism, biologic behavior, and therapeutic model of human DSRCT.

Chromosomes that show partial loss or gain in near-diploid tumors coincide with chromosomes that show whole loss or gain in near-triploid tumors: evidence suggesting the involvement of the same genes in the tumorigenesis of high- and low-risk neuroblastomas.

We performed two‐color fluorescence in situ hybridization analysis to detect the numbers of chromosomes 1 and 17, 1p deletion, and 17q gain in 177 neuroblastomas, including 101 tumors that were found by a mass‐screening program for infants. Sixty‐eight tumors with disomy 1 or tetrasomy 1 were classified as the Dis1 group, and 109 tumors with trisomy 1, pentasomy 1, or a mixed population of cells with trisomy 1 and cells with tetrasomy 1 were classified as the Tris1 group. 17q gain was the most frequent genetic event, followed by 1p deletion, and MYCN amplification in both Dis1 and Tris1 tumors. However, the incidence of all the genetic events was higher in Dis1 tumors than in Tris1 tumors. These findings suggest that Tris1 tumors are more resistant to acquiring the genetic events than are Dis1 tumors. In addition, there was an accumulation of genetic events in more advanced stages, with the exception of a high incidence of 17q gain in the stage IVS Tris1 tumors. Comparative genomic hybridization analysis, which was performed in 59 of the 177 tumors, showed that chromosomes partially lost or gained in Dis1 tumors coincided with chromosomes totally lost or gained in Tris1 tumors. Dis1 and Tris1 tumors were considered to have near‐diploid/tetraploid and near‐triploid/pentaploid chromosome numbers, respectively. These findings suggest that the same tumor‐suppressor genes or oncogenes may be involved in the development and progression of both high‐ and low‐risk neuroblastomas, and that the ploidy state of the tumor plays a fundamental role in the heterogeneous behavior.

Synovial sarcoma with a secondary chromosome change der(22)t(17;22)(q12;q12)

A consistent, pathognomonic translocation, most commonly a balanced reciprocal translocation, t(X;18) (p11.2;q11.2), is found in more than 90% of synovial sarcomas. We report here a secondary chromosome change, der(22)t(17;22)(q12;q12), in addition to the primary t(X;18)(p11.2;q11.2) in a biphasic synovial sarcoma that occurred in the thigh of a 34-year-old woman. Although the karyotype of the primary tumor exhibited 46,X,t(X;18)(p11.2;q11.2), the recurrent tumor showed 46,X,der(X)t(X;18)(p11.2;q11.2),der(22) t(17;22)(q12;q12). The SYT-SSX1 fusion transcript was demonstrated in the primary and recurrent tumors using a reverse transcriptase polymerase chain reaction (RT-PCR). Southern blot analysis also confirmed that the detected messages were derived from the SYT-SSX fusion gene. However, we could not detect the EWS-E1AF fusion gene that has been reported to be generated through a t(17;22)(q12;q12) by RT-PCR. Furthermore, fluorescence in situ hybridization (FISH) with cosmid probes corresponding to loci flanking the EWSR1 region demonstrated no split of chromosome 22 in all analyzed interphase nuclei. To our knowledge, this is the first reported case of synovial sarcoma in which an additional (secondary) chromosome change, der(22)t(17;22)(q12;q12), has been demonstrated.