Many tumour types have been reported to have deletion of 9p21 (refs 1-6). A candidate target suppressor gene, p16 (p16INK4a/MTS-1/CDKN2), was recently identified within the commonly deleted region in tumour cell lines. An increasing and sometimes conflicting body of data has accumulated regarding the frequency of homozygous deletion and the importance of p16 in primary tumours. We tested 545 primary tumours by microsatellite analysis with existing and newly cloned markers around the p16 locus. We have now found that small homozygous deletions represent the predominant mechanism of inactivation at 9p21 in bladder tumours and are present in other tumour types, including breast and prostate cancer. Moreover, fine mapping of these deletions implicates a 170 kb minimal region that includes p16 and excludes p15.

The cellular origin ol the sarcomatous component of gliosarcomas is controversial. It is not clear if the sarcoma arises in transition Irom the glial cells that comprise the gliomatous component or independently arises from non-neoplastic mesenchymal cells oí the tumor stroma. Using comparative genomic hybridization (CGH) along with cytogenetic analysis, fluorescence in situ hybridization (FISH) analysis, and polymerase chain reaction (PCR) analysis of microsatellite allelic imbalance, we have evaluated the genetic alterations in the gliomatous and sarcomatous components of five gliosarcomas. The glial element was grade 4 librillary astrocytoma (glioblastoma multiforme) in all five tumors. The sarcoma elements were fibroblastic without osseous* chondroid, or angiosareomatous differentiation. Gain of chromosome 7, loss of chromosome 10, deletions of the chromosome 9 p-arm. and alterations of chromosome 3 were frequently observed, demonstrating that gliosarcomas can be genetically classified as belonging to the spectrum of glioblastomas. Furthermore, the sarcomatous and gliomatous portions of each gliosareoma investigated were similar with respect to both the presence and absence of specific genetic alterations. This observation supports the hypothesis that the sarcomatous component of a gliosareoma either arises from the same common precursor cell as the gliomatous portion, or it arises from the gliomatous portion itself.

Cytogenetic studies may provide important clues to the molecular pathogenesis of thyroid neoplasia. Thus, the authors attempted cytogenetic studies on 12 thyroid carcinomas: seven papillary, three follicular, and two anaplastic. Successful cytogenetic results were obtained on all 12 tumors; nine (75%) had one or more chromosomally abnormal clones. Four of the papillary carcinomas had a simple clonal karyotype, and three had no apparent chromosome abnormality. All four abnormal papillary tumors contained an anomaly of a chromosome 10q arm. In one instance, an inv(10)(q11.2q21.2) was observed in a Grade 2 papillary carcinoma as the sole acquired abnormality. In another case, an inversion or insertion involving 10q21.2 was found in a Grade 1 papillary tumor. The karyotype of a third tumor, a Grade 1 papillary carcinoma, was 46,XX,der(5)t(5;10)(p15.3;q11),der(9)t(9;?)(q11;?). A fourth abnormal papillary carcinoma, a Grade 1 tumor, had a t(6;10)(q21;q26.1) as the sole abnormality. Each of the five follicular or anaplastic carcinomas had a complex clonal karyotype. The three follicular carcinomas contained an abnormality of 3p25-p21, along with several other chromosome abnormalities.

Conventional cytogenetic studies have suggested that trisomy 12 may be a characteristic nonrandom numerical chromosome anomaly in benign ovarian tumors, particularly sex cord-stromal tumors. To confirm this finding, and to avoid possible culture artifact introduced during cytogenetic analysis, the authors performed fluorescence in situ hybridization (FISH) in paraffin-embedded samples of select ovarian neoplasms. Forty-four ovarian fibromas and granulosa cell tumors and 31 benign and borderline epithelial ovarian tumors were examined for the presence of trisomy 12. Trisomy 12 was detected in 40% (8 of 20) of the fibromas. No evidence of trisomy 12 was present in 24 granulosa cell tumors, although 1 granulosa cell tumor was tetrasomic for chromosome 12. Trisomy 12 was found in 27% (3 of 11) of the serous borderline tumors, but was not observed in any of the benign epithelial tumors (13 serous and 7 mucinous cystadenomas). These results confirm that trisomy 12 occurs in a significant proportion of fibromas. However, the incidence of trisomy 12 in granulosa cell tumors is far lower than suggested by previous studies. These results, in conjunction with those of previous cytogenetic reports, suggest that trisomy 12 is rare in benign epithelial ovarian tumors, but occurs fairly commonly as a sole anomaly in borderline epithelial tumors. Further investigation is necessary to establish the significance of trisomy 12 in the pathogenesis of these tumors.

We studied cells from 30 controls and 85 cases of untreated B-chronic lymphocytic leukemia (CLL) with a fluorescence in-situ hybridization (FISH) technique utilizing a probe to chromosome 12. By use of a threshold of > 2% for trisomy 12 for the CLL cases (the mean +3 SD for controls was 1.3%), 20% (17/85) were trisomy 12. The mean % cells positive was 32.6 (median, 39.4; range, 2.4-79.1). There was a trend toward an higher incidence of trisomy 12 in patients with Rai stages 1-4 vs Rai 0 (p = 0.16). Forty-seven % (8/17) of patients with trisomy 12 had strong intensity CD20 antigen expression compared to 21% (14/68) of patients without trisomy 12 (p = 0.03). Trisomy 12 associated with CLL is easily detected by FISH with an overall incidence of 20%. This technique should be applied to larger groups of patients to confirm the potential variation among Rai stages and immunophenotypic subgroups.