50

observed repeatedly during 40 culture passages. The presence of metaphase spreads showing evidence of endoreduplication suggested this as a likely mechanism for the doubling of chromosome number per cell. Eleven marker chromosomes were observed in Ihe cells of the primary sample; these markers persisted through all subsequent pas- sages. Chromosomes 1, 2, 6, 7, 8, 11, and 16 were consislenlly overrepresented; each of these chromosomes was Involved in marker formation. Chromosomes 4,5,9, 10, 19,21, and 22 were consistently underrepresented. Every chromosome, either in its normal form and/or as part of a marker, was reprcsentcd on the average by at least one copy per diploid cell. Eighteen new marker chromosomes were observed during the course of cell cultivarion; one of these evolved into a clonal marker over the course of six cell passages. Of the new marker chromosomes that were formed during the observation period, the majority were found in hypotetraploid cells.

Lack of expression of aminoacylase-1 in small cell lung cancer. Evidence for inactivation of genes encoded by chromosome 3p Miller YE, Minna JD, Gazdar AF. Deparrmenr ofMedicine, Veterans AdministraGon Medical Cenrer, Denver CO 80220. J Clin Invest 1989; 83:21204.

A deletion involving chromosome 3p (14-23) characteristically occurs in small cell lung cancer (SCLC). Reduction to homozygosity, rather than complete loss, is typically observed for genes in the deleted region. Lack of expression for gents encoded by this region, implying inactivation of all alleles, has not been previously described. We have examined the expression of aminoacylase-1 (ACY-I), encoded by chromosome 3~21, using both an electrophoretic activity assay and a monoclonal antibody-based ELISA. A variety of human tissues, includ- ing lung, brain, liver, kidney, heart, adrenal medulla, and eryrhrocytes have previously been tested for ACY-1 activity and antigen; all but erythrocytes are positive. Thus, ACY-1 is expressed in all nucleated human cells examined to dale. ACY- 1 was undetectable in a significant number of SCLC cell lines (4/29) and tumors (l/8), but not in non-small cell lung cancer (NSCLC) cell lines (O/19) or tumors (O/9), nor in a variety ofothcrhuman cell lines (O/15) or colon lumor(0/8). Inaddition, reduced(_lO%ofnormal)ACY-1 expressionwascommoninSCLCcel1 lines (14/29) and tumors (3/8), but not in NSCLC cell lines (l/19) or tumors (O/9), nor in other human cell-lines (O/15) or colon tumors (O/P). Thus, low or undetectable ACY-1 expression is highly specific for SCLC and occurs in both ccl1 lmcs and tumor tissue. The finding of undetectable ACY-1 expression in SCLC supports the hypothesis that inactivauon of all alleles of specific chromosome 3p genes occurs in SCLC in a fashion analogous to Rb gene Inactivation in retinoblastoma, and suggests that the strucmral gene for ACY-1 may be closely linked Lo a putative SCLC tumor suppressor gent.

Expression ofthesmall carcinoma antigensofcluster-5 andcluster- 5A in primary lung tumours Maier A, Schmidt U, Waibcl R, Hartung W, Srahel RA. Instirure of Pathology, Ruhr University, 4630 Bochum. Br J Cancer 1989;59:692- 5.

The expression of the small cell carcinoma (SCLC) antigens cluster- 5(antibodyLAMB)andcluster-5A(antibodySWA20)wasexaminedon a panel of routinely processed biopsy or surgical specimens of 290 lung tumors by lmmunoperoxidase staming. Antigen expression was largely restricted to SCLC. Of over 150 tissue samples evaluated, moderate or strong antigen expression was found in 49% (cluster-5) and 45% (cluster-5A). Concordance in expression of the two antigens was seen in 71% of SCLC samples, with 35% expressing both antigens strongly, 8% moderately and 28% being negative for both antigens. Antigen expression was independent of the morphological subtype of SCLC. Primary lung tumours of other histology, including squamous cell carcinoma, large cell carcinoma, adenocarcinoma, mesothelioma or carcinoid had no sigmficantantigcn expression. Of 135 tumours, strong

or moderate expression of both antigens was seen only m two cases. 20%, mostly carcinoids, wcrc weakly positive for cluster 5 and 4% for cluster5Aantigen.Theremainderwereanligennegative. Nosignificant antigen expression was seen in 25 normal lung tissues. The membrane antigens of SCLC cluster 5 and 5A arc markers for SCLC and their expression in tissues is tumour-associated.

Expression and amplification of myc gene family in small cell lung cancer and its relation to biological characteristics Takahashi T, Obata Y, Sekido Y et al. Deparment ojThoracic Surgery, Nagoya University School ofMedicine, Showa-ku. Nagoya466. Cancer Res 1989;49:2683-8.

Eighteen small cell lung cancer (SCLC) lines (including nine lines established by this group) z well as 3 1 tumor samples from 23 SCLC patients were examined for Ihe surface amigen phenotype and the expression and amplification of the myc gene family. The expression of NE-150 ncuroendocrine, PE-35 pancpithchal and OE-130 epithelial antigens corresponded well with the level of biomarkers of SCLC lines, i.e., the NE-lSO+/pE-35+/OE-130 phenotype corresponded to classic type, while the other phenotypes such as NE-15O+/PE-35./OE-130 to variant type. In tumor specimens, most classic SCLC (consisting ofoat cell type and intermediate ccl1 type, subtype a) showed NElSO+/PE- 35+/OE-130.phenotype. whilcsmallccll-largccellcarcinoma(in~erme- diate cell lype, subtype b) expressed various phenotypes. The amplifi- cationofrhemyc gene family wasobscrvedin nineoutof 18lines(50%) and five out of 23 patient tumors (22%~). Higher levels of expression of eilhcrc-myc, N-myc,orL-myc wcrcdctcctedin lhoutof 18lines(89%) and m five out of six patient tumors (83%), when compared with that of normalorfetal lung lissucs. Thus, the higherexpression withoutobvious myc gcnc amplification was obscrvcd. The ccl1 lines and tumor with the amplified myc always exprcsscd their corresponding myc genes. The rcsul& suggested thathighcrlevelsofexprcssionofthemycgenefamily may play a significant role in the oncogcncsis of SCLC. Amplification and/or high levels of expression of c-myc were observed not only in variant type SCLC lines, but also in classic type lines. Thus, they were not necessarily associated with distinct biomarkers of SCLC lines.

Genetic changes in the pathogenesis of lung cancer Birrer MJ, Minna JD. NCI-Navy Medical Oncology Branch and Uni- formed Services University of the Health Sciences, Naval Hospiral and National Cancer Institute, Bethesda, MD 20814. Annu Rev Med. 1989;40:305-17.

Human lung cancer is a complex genetic disease resulting from a series of inherited and somatically occurring defects in a number of critical genes. These genetic events, produced in part by carcinogen exposure, includechromosomaldclction,rcarrangemen~,andmutation, andlead toinactivationoractivationofcertain targetgenes. Recentdata showed these genes to mcludc both recessive oncogenes such as the retinoblasroma gene and dommamly acting oncogenes such as the myc and ras family members.

Action potentials of cultured human oat cells: Whole-cell measure- ments with the patch-clamp technique Johansson S, Rydqvist B, Swcrup C, Hcilbronn E, Arhcm P. Nobel lnsritule for Neurophysiology, Karohnska Instmre~, S-104 01 Slack- helm. Acm Physiol Stand 1989;135:573-8.

Oat cells (of the small ccl1 carcinoma of the lung) have been rcportcd togeneratecalciumactionpotentials.Thecalciumchannels havefurthcr been suggested to play a crucial role in the relation between oat cell carcinoma and the often associated myasthenic syndrome. WC have examined cultured human oat cells (U-1690) under volfagc-clamp conditions, using rhe patch-clamp technique. WC found, contrary to previous repor&, that the action potential was caused by sodium and potassium currents. No calcium current was detected under these