Loss of heterozygosity in human ductal breast tumours indicates a recessive mutation on chromosome 13

Meeting Abstracts

1776

cytoskeletal proteins.lbesemcdificaticcs againmimicthoseseenintbaeabryoduring aqarable stagesof differentiation. RRcoEmmoF-

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lXESRNGFIPROSISAETER

RADIUEIIWGY F.Mki& V.Sim&& R.Zorc,P&as, rUkiMk,M.VorzeljandE.Kansky The Institute of Yugcelavia

oncolcgy,Ljubljana,

Ten beagle dogs (femaleand male), weight 10 to l2kg,lto2yearsoldwere irradiatedwith Gy (Cobalt-Phillips) onto the whole pelvisski tail for 20 days. Platinolwasgivenin a 2 kur infusicm 5 days for 20 days during the Tendogsrepresentsda Ezzmreatlsanti controlgroup. Ten dayslaterthe thoracic ductlynphocytes, peripheralblocdandthe large intestinewere examimd with the following parametis: laboratory, ml, biochemical, histolcgical, RR, inmnolcgical, and LMMA 500 densitanetric, examinaticns.Dmage aud rsmdellingof peripheralblood lyqkcytes,tbxacicduct lympkqim, entero-errlocrine cells, mast in the intestinal cells and l_ smsars of thelaminapropriawerefaundin all treated dogs. OTspecia1intfxestwas enhaxed volume density of mast- aId cells, that could also ~tero_endarCine reflectenhanc& serotoninexcr&ion,with hypoxiaof the intestinaltissue. LAWA 500 measurmentsestablishedsiguificantchaqes intheorganic ampositicnof the lamina Propria cells. Imrmnologicalstudies significantly diminished revealed tmnsfomation of 1ympkcyteswithPRAarkd Con-Astimulation in the treatedgrcup.It is cmsideredthatthechangesdescribed represent a stimulus for fikmgen hyperpmducticn andcollagenexcretionin thekeatedgrcupofdogs.

L.R.Iml(l), A.Ricci.o(2), P.A.m(l), L.S.Nielssn(l), P.Rristaem(l), M.Iaibo(3), O.Saksela(3), P.=asU2) a R.DaWl) (l)Finsen Laboratory, Rigshospitalet, (2)Interuati~l of -k; Genetics and Biophysics, of Naples, Italy; and (3)Departmentz virology, university of Helsinki, Fink& Ey

Ihemechauimsbehibdatramfo7.ming gravth factor-betaUGF-beta) i.IYduced stinnllatialof pxodu&icm of type-l plamimgm activatorinhibitor (PAI- in have been WI-38 human luug fibrcblasts studiedusinga full-leqthcLNAprobefor PAI-I, as well as mnocloM1 antibodies againstthe inhibitor.Northernarddot blot analyses shcx+&that!EF-beta causesau eaL-lyimrease in thePAI-1 lIRNAlevel, enhancementafter8hr. of protein synthesis With x a 5o-fo1d cycl~e caused an eguallystrong in ths level of PAI-I nmA. Weal studiesofthe Ezzive effectof IGF-betam PAI-Iprotein levels in cell extractsandculturemsdia were consistentwiththeeffect on PAI-I mRNA. The results suggestaprimaryeffectof TGF-beta on PAI-Igenetranscription. mSSoFImERozMosITYIRRuMAR~ Mmsl!lurmJRS INXCAIRS A WrATIoRoR cIRKmmm 13 m%ri.tm _(I), NonWsWWl)

RElcEssIvE

m&Jert samod2) ad

mmls

of clinicalGeneticsand (lNk@Hmnts (2)Tmour Pathology,KarolinskaRospital, 2-10401Stockholm, Sweden at chmmsa& loci ~genotypes definedby LemMMntmprobesrevealing restriction fragmentklgth polymorphisms weredetemimd inconstituticnaltitmcur tissue fran 10 cases of ducta1lxeast caucer:eight p?zmmpausalfealalesandtwo males. Samtic loss of coustitutiom1 hetmoqgosity was obsemed at loci cm C%mKmmel3in primarytl.amurtissuefran threefsmalesaudonemale. Intwocases, specificloss of hetemqqosity at three distinctgeneticlocialaqthe lmqth of thech?mmmxwasobserved.Inanother cmcument lossof allelesat locim ECEkeam 2, 13, 14 and 20 was detected, shCx& loss of while afourthcase heterosygosityforchramsanes5andl3. In eachinstance,thedatawereconsistentwith lossofoneof thehcmlogcus~by mitoticnondisjunction. Analysis of locion sevexalother chmmosanesshcW&retention of ccnstituticmal hetcxozygosity suggesting the relativespecificity of the events. Thesedataindicatethatthepathogeuesisof ductalbreastcancer may,inasubstantial prcportianofcases, involveunmaskirrgofa recessivelccusonchranosme13. BY WIiICEl lW DIFFERIN MSCHANIS IRRSINDDcFlmLRS1ais 5-FLCK.uoPYRIMID Dlf~andSigridI&tl