Detection of deletional events in lung cancer by fluorescence in situ hybridization

149

Abstracts

A35 I-T Yu,

MONOSOMY FOR CHROMOSOME 22 IN REABDOID TUMORS OF TEE BRAIN BY FLUORFXENCE M SlTU IlYBRlBlZATION PC

A36

DETECTION OF DELETIONAL EVENTS IN LUNG CANCI: R BY FLUORESCENCE IN SITU HYHRIDIZATION. Marileila Varella-Garcia’. Ron F. Suijkerbuijk’. Harry A. Drabkin’.‘. Robert M. Gemmill’. University of Colorado Cancer Center, Box 8188, 4200 E 9th Ave, Denvnr CO 80626; ‘Eleanor Roosevelt Insthti~e. 1899 G- :rd St, Denver CO 80206. USA.

Burger, CA Griffin J5.JPerlman. and the Pediatric

Oncology Group. The Johns Hopkins Hospital, Baltimore, Maryland Rhabdoid tumors (RT) of the central nervous system (CNS) are rare aggressive tumors of infants, most commonly involving the cerebellum. Studies have shown monosomy 22 to be present in a smsll number of CNS RT, however the frequency of this abnormality is unknown. Furthermore, the liits of the histologic spectrum of CNS RT have not been explored. We examined 10 CNS RT

Lunq cancer is one of the most common causes of cancer deaths in the world. Although surgical resections, radia’nrl and chemotherapy can achieve objective respcI.- ‘5 in 1~‘; cancer patients, the high incidence and poor prognc’ : prompt hopes that early detection and more effective interventions will help to reduce mortality rates. R,lmerous cytogenetic and molecular genetic studies have reported that in virtually all smallcell lung carcinomas (SCLC) and about 75 percent of non-small-cell lung carcinomas (N-SCLC) the short arm of human chromosome 3 (3p), especially 3~13, 3~14.2 and 3~21.3. undergoes deletional events. Objective data, such as a 3p marker loss. may provide a powerful adjunct to the subjective interpretations now used to clinically evaluate biopsies and sputa. Fluorescence in situ hybridization (FISH) techniques provide a powerful tool for a relatively simple, rapid and sensitive detection of chromosome aberrations in tumor cells. Furthermore, FISH is ideally suited for analysis of single, interphase cells and can greatly contribute to insights into tumor heterogeneity. We are testing cosmid probes derived from the three 3p regions for FISH analysis of established SCLC and N-SCLC cell lines. Our preliminary results suggest that FISH can be a reliable test to screen for deletional even& in these 3p regions in lung tumor cell lines. Currently we are applying this approach to tumors and early lesions.

following review of histology and immunohistochemistry Most of these tumors had been previously classified as medulloblastoma Histologic features of RT included necrosis. rnitotic activity, and a Although there were areas showing only jumbled architecture primitive cells, generally the cells were large relative to those of medulloblastomaand contained large nuclei with prominent nucleoli Cytoplasm was prominent in some areas. As a group, the tumors were immunoreactive for epithelial membrane antigen, vimentin giial fibriilsry acidic protein and cytokeratins. Scattered cells in some cases

were reactive for chromogranin and synaptophysin as well as actin Fluorescencein situ hybridiiion was performed on interphase cells of disaggregated para%& material with a paint probe to chromosome 22 (Oncor) Of IO RT tested. 8 were interpretable. and 7 showed evidence of monosomy 22; one case showed three unequal signals. consistent with a translocation involving chromosome 22, confirmed by cytogenetic analysis We conclude that abnormalities of chromosome 22 are common in CNS RT There appears to be a histologic spectrum of RT, varying from a primitive small blue cell tumor similar to medulloblastoma to a tumor with larger cells with prominent cytoplasm Therefore, in infants with a primitive tumor in the fourth ventricle, RT should be considered. in tight of the almost uniformly poor prognosis of the RT.

CYTCGENETIC ANALYSIS A37 MARROWS: CORRELATION

OF SERIAL BONE WITH CLINICAL STATUS.

L.R. Adam’, L.C. Sheppard’, P. Zollars’, H.H. Hobart’ ‘Palo Verde Laboratory, Chandler, AZ. ‘Clin-Path Associates. Phoenix, AZ. Serial cytogenetic analysis of bone marrow cells throughout the neoplastic course provides important informatlon regarding disease status and prognosis. Whether the karyotype of the diagnostic sample is normal or abnormal, the appearance 01 additional abnormalities, or a new abnormal cell line, is indicative of disease progression, Clonal evolution in chronic myelold leukemia, for example, is usually associated with progression to acute leukemia. and the nature of the new karyolypic changes helps to identify the lineage involved in blast crisis (lymphoblastic or myeloblastic) Clonal evolution is closely associated with the onset of relapse In acute myeloid leukemia, often before there is clinical evidence, and early therapeutic intervention IS possible. As cytogenetics is not a very sensitive tool in detection of low-level residual disease, it is not always useful in predicting disease regression. although disappearance of a previously detected abnormal cell line is associated with good prognosis. Serial cytogenetic analysis throughout therapy for AML and myebdysplasia allows assessment of the effectiveness of

A38

Reinterpretation of Gbanding Complex Karyotypes by Fluorescence In Situ Hybridization with Chromosome-specific DNA Libraries and Alphasatellite Centromere-specific DNA Probes in malignant Hematological Disorders Guangping Kurt *

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