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Several chromosome regions exhibit loss of heterozygosity (LOH) in human breast carcinoma and are thought to harbour tumour suppressor genes (TSG). At chromosome 13q, two TSGs have been identified, RB1 at 13q14 and BRCA2 at 13q12-q13. In this study, 139 sporadic breast tumours were analysed with 18 polymorphic microsatellite markers for detailed mapping of LOH at chromosome 13q and evaluation of an association with known progression factors. LOH with at least one marker was observed in 71 (51%) of the tumours analysed. The deletion mapping indicated three LOH target regions, 13q12-q13, 13q14 and 13q31-q34. LOH at chromosome 13q12-q13 was associated with low progesterone receptor content, a high S phase fraction and aneuploidy. Multivariate analysis adjusting for lymph node involvement and S phase fraction showed that patients with tumours exhibiting LOH at 13q12-q13 have a 3-4-fold increased risk of recurrence and death compared with other patients. Our results suggest there are at least three separate LOH target regions at chromosome 13q and inactivation of one or more genes at chromosome 13q12-q13 results in poor prognosis for breast cancer patients.

O-acetylated and non-O-acetylated sialoglycoproteins can be distinguished by the mPAS (mild periodic acid-Schiff) histochemical technique. Individual adults show one of three different patterns of staining of large intestinal mucosa: uniformly mPAS-positive, uniformly mPAS-negative, or mPAS-negative with scattered mPAS-positive crypts. To test our hypothesis that these variations are the result of a single autosomal gene (oat) polymorphism, we have studied the frequency of the three patterns of staining in a total of 435 adult colon specimens from six geographically separate populations: British, South African blacks, Icelanders, Japanese, Hong Kong Chinese, and Bahrainis. The distribution of the three types of staining fell into two groups. In Japanese and Chinese, uniformly mPAS-positive cases were much more frequent than uniformly mPAS-negative cases; this distribution differed significantly (chi 2, P < 0.001) from that in non-Sino-Japanese, where the uniformly mPAS-positive phenotype was much less frequently found than the uniformly mPAS-negative phenotype. In neither of the groups did the frequency of the three phenotypes differ significantly from that predicted for a single gene polymorphism by the Hardy-Weinberg law. The variation in staining patterns between populations is consistent with variation in frequency of a single polymorphic autosomal gene (oat) controlling O-acetylation of sialic acid, probably by an O-acetyl transferase enzyme. Loss of function mutation in the high acetylator gene (oata) in a colonic crypt stem cell in heterozygous individuals would account for the scattered discordant crypts. Gene frequencies for a variety of enzymes differ between the Sino-Japanese and non-Sino-Japanese races.(ABSTRACT TRUNCATED AT 250 WORDS)

Reykjavik 1978Scand Cardiovasc J Downloaded from informahealthcare.com by University of Newcastle Upon Tyne on 12/03/14For personal use only. Printed in Iceland Fklagsprentsmi8jan hf. -Reykjavik 1978 Scand Cardiovasc J Downloaded from informahealthcare.com by University of Newcastle Upon Tyne on 12/03/14 For personal use only. Lzknadeild Haskdla islands hefur a fundi sinum 31. mai 1978 sampykkt ad taka ritgerd pessa gilda ti1 doktorsprd fs. d l a f u r ~l a r n a s o n deildarforseti. Scand Cardiovasc J Downloaded from informahealthcare.com by University of Newcastle Upon Tyne on 12/03/14 For personal use only. Scand Cardiovasc J Downloaded from informahealthcare.com by University of Newcastle Upon Tyne on 12/03/14 For personal use only. PREFACE During the collection of material and latr? whilst writing the present monograph I was engaged as a thoracic surgeon at the Department of Thoracic Surgery, Landspitalinu (University Hospital), Reykjavik, and as such had the privilege of access t o the hospital records and other facilities for which I am most grateful. Close co-operation with physicians, both district physicians, general practitioners, ant1 chief physicians of the hospitois, besides other personnel engaged in th? health service throughout the country, has made this project the more agreeable, and I a m most indebted t o them. I a m also very grateful for the excellent co-operntion i,nd kind response o f the people included in the present material whilst performing the follow-up examinutions. Porgeir Porgeirsson, M D , c!t the Institute of Pathology, assisted in stzldying the histological preparations. , assisted in the measurement of the chest X-ray films. Ott6 J . Bjornsson, cand. stat., lecturer at the University of Iceland, assisted with the statistical computation. Professor emeritus J u l l u s Sigurjbnsson, reud through the manuscript and gave much valuable advice. Peter Cahill, B. Litt., lecturer at the English Department, University of Iceland, revised the English translation. T h e Board of the State Hospitals supported the project concerning followup radiological examination. T h e Icelandic Research Foundation granted financial support for t w o !/ears. For the publication of the paper financial support was given b y the /Ministry of Health. T o all those mentioned above, and to many others w h o in various ways have assisted m e I extend m y sincerest gratitude for their invaluable help and co-operation. Finally, m y deepest thanks to mu w i f e , b6rdis Porvaldsd6ttir, BA, librwian, who from the v e r y beginning has helped m e w i t h this project b y discussing the problems,collecti n g references, and doing all the typing; without her help and enthusiasm :his project could not have been completed. Reykjavik, June 26th) 1978. Jon G. Hal1,grimsson. Scand Cardiovasc J Downloaded from informahealthcare.com by University of Newcastle Upon Tyne on 12/03/14 For personal use only. Scand Cardiovasc J Downloaded from informahealthcare.com by University of Newcastle Upon Tyne on 12/03/14 For personal ...

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