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LEUKÆMIA AND LOSS OF Y CHROMOSOME
506 conditions. These results might be taken to mean that the medical use of ultrasound is harmless from the genetic viewpoint. Nevertheless, even much lower doses have a drastic effect on purified D.N.A.8 H. GALPERIN-LEMAITRE Laboratoire de Génétique médicale, P. GUSTOT. Université Libre de Bruxelles. Clinique Obstétricale et Gynécologique, Hôpital Universitaire Brugmann, Brussels, Belgium.
S. LEVI.
LEUKÆMIA AND LOSS OF Y CHROMOSOME SIR,-Sandberg and Sakurai9 suggested that cells without a Y chromosome may never be involved in acute leukaemia, but may play a role in the pathogenesis of the neoplasia. Pierre and Hoagland 10 hold a different view about the role of the missing Y in acute leukaemia. 3 male patients with chronic myeloid leukaemia (C.M.L.) had a variable proportion of 45,X(Ph’, Y[-)) cells. Their clinical condition was stabilised and the leucocyte alkaline phosphatase (L.A.P.) rate was 21-42% positive neutrophils (higher than in C.M.L., 0-5% positive neutrophils). Granulocytes formed 63-88% of a total white count of 6100-29,000 per c.mm. Two other men with lung cancer had a 45,X karyotype. Their clinical condition was poor and the L.A.P. rate was 69% and 86% positive neutrophils. The granulocytes were 71-85% (white cells 14,200-62,000). These cases lead us to hypothesise that: (1) an interchromosomic Ph’/Y effect may exist (Y-chromosome loss had a temporary favourable effect on the C.M.L.); (2) the isolated Y loss may cause a karyotype imbalance and may have a bad effect on lung cancer. J. GROZDEA A. KESSOUS I.N.S.E.R.M. (U. 100), P. COLOMBIES. Toulouse 31300, France.
RETINOBLASTOMA: CHROMOSOME BANDING IN PATIENTS WITH HERITABLE TUMOUR
SIR,-20% of patients (8 of 40) with Dq-deletion reported in the literature have developed retinoblastomas.11-21 6 of these patients had bilateral tumours diagnosed in the first year of life, which is characteristic of inheritable retinoblastoma as defined by Knudson.22 In 4
cases
in
which the
deleted
chromosome
was
adequately studied by radioautography or by the new banding techniques, chromosome 13 was affected. In 2 of these cases the deletion involved an interstitial portion amounting to about a quarter of the long arm of Dn. D13 has two broad darkly staining bands in the mid to distal portion of the long arm with additional narrow dark bands 8. 9. 10. 11.
Galperin-Lemaître, H., Levi, S., Kirsch-Volders, M. Unpublished. Sandberg, A. A., Sakurai, M. Lancet, 1973, i, 375. Pierre, R. V., Hoagland, H. C. ibid. p. 1008. Allerdice, P. W., Davis, J. G., Klinger, H. P., et
al. Am. J. hum. Genet. 1969, 21, 499. 12. Gey, W. Humangenetik, 1970, 10, 362. 13. Grace, E., Drennan, J., Colver, D., Gordon, R. R. J. med. Genet. 1971, 8, 351. 14. Kahn, J., Reed, F. ibid. p. 372. 15. Laurent, C., Noel, B., David, M. Ann. Genet. 1971, 14, 33. 16. Lele, K. P., Penrose, L. S., Stallard, H. B. Ann. hum. Genet. 1963, 27, 171. 17. Orye, E., Delbeke, M. J., Vandenabelle, B. Lancet, 1971, ii, 1376. 18. Taylor, A. I. Humangenetik, 1970, 10, 209. 19. Thompson, H., Lyons, R. B. Hum. Chrom. Newsletter, 1965, 15, 21. 20. Wilson, M. G., Melnyk, J., Towner, J. W. J. med. Genet. 1969, 6, 322. 21. Wilson, M. G., Towner, J. W., Fujimoto, A. Am. J. hum. Genet. 1973, 25, 57. 22. Knudson, A. G. Proc. natn. Acad. Sci. U.S.A. 1971, 68, 820.
proximal and distal to these broad bands. The second distal broad band is deleted in the cases of Orye et al.17 and Wilson et a1.20,2l and is tentatively designated del (13) (q22::q32). Pruett and Catkins 23karyotyped 21 patients with retinoblastoma (17 sporadic, 4 bilateral) by standard techniques and were unable to show any chromosomal abnormality. Because of the devastating nature of this tumour, we chose to re-evaluate some of their patients using the newly developed trypsin banding technique of Seabright,24 in the hope of finding a consistent chromosomal-banding anomaly which might prove useful in prenatal diagnosis. Our patients included 7 with bilateral retinoblastomas (mother and daughter; mother, daughter, and son; two isolated bilateral tumours) and 5 with sporadic unilateral tumours. At least 5 cells with optimal banding
more
or more
were
studied in each
case.
None of the karyotypes of our patients showed a D-group deletion, the banding patterns being identical to those found in patients without retinoblastoma. Specifically, group-D chromosomes uniformly showed the presence of the major band on 13q which was reported as deleted in the two 13q cases noted above. A typical set of D-group chromosomes from one of our patients is shown in the figure. Technical variation in the number of visible bands
routinely occurs from metaphase to metaphase in any one preparation, presumably because of different conditions of chromosome contraction, and, furthermore, slight differences
of number and size of bands between
a
chromosome
pair in a given metaphase are the rule. Our patients had none of the major congenital malformations often found in Dq patients. Only one child in this study with bilateral tumour has moderate mental retardation and unusual facial and hand features. Review of additional metaphases from this patient failed to show a deletion or banding aberration.
Thus, these studies fail to demonstrate any abnormality of the bands on the D-group chromosomes in patients with bilateral retinoblastoma. It remains quite possible that most cases of retinoblastoma result from a single gene mutation on 13q while only some are caused by visible chromosomal aberrations there. Conversely, not all Dq patients develop retinoblastoma, and some probably involve not chromosome 13, but 14 or 15. Specific chromosome identification and banding in the Dq patients will be required to solve this uncertainty and to determine whether the same kind of deletion occurs in all 13q patients with retinoblastoma. Genetics Unit, Children’s Service, Massachusetts General Hospital, Harvard Medical School, Boston, Mass. 02114, U.S.A. 23. Pruett, R., Atkins, L. Archs Ophthal. 1969, 24. Seabright, M. Lancet, 1971, ii, 971.
R. LADDA L. ATKINS J. LITTLEFIELD R. PRUETT. 82, 177.
S. LEVI.
LEUKÆMIA AND LOSS OF Y CHROMOSOME SIR,-Sandberg and Sakurai9 suggested that cells without a Y chromosome may never be involved in acute leukaemia, but may play a role in the pathogenesis of the neoplasia. Pierre and Hoagland 10 hold a different view about the role of the missing Y in acute leukaemia. 3 male patients with chronic myeloid leukaemia (C.M.L.) had a variable proportion of 45,X(Ph’, Y[-)) cells. Their clinical condition was stabilised and the leucocyte alkaline phosphatase (L.A.P.) rate was 21-42% positive neutrophils (higher than in C.M.L., 0-5% positive neutrophils). Granulocytes formed 63-88% of a total white count of 6100-29,000 per c.mm. Two other men with lung cancer had a 45,X karyotype. Their clinical condition was poor and the L.A.P. rate was 69% and 86% positive neutrophils. The granulocytes were 71-85% (white cells 14,200-62,000). These cases lead us to hypothesise that: (1) an interchromosomic Ph’/Y effect may exist (Y-chromosome loss had a temporary favourable effect on the C.M.L.); (2) the isolated Y loss may cause a karyotype imbalance and may have a bad effect on lung cancer. J. GROZDEA A. KESSOUS I.N.S.E.R.M. (U. 100), P. COLOMBIES. Toulouse 31300, France.
RETINOBLASTOMA: CHROMOSOME BANDING IN PATIENTS WITH HERITABLE TUMOUR
SIR,-20% of patients (8 of 40) with Dq-deletion reported in the literature have developed retinoblastomas.11-21 6 of these patients had bilateral tumours diagnosed in the first year of life, which is characteristic of inheritable retinoblastoma as defined by Knudson.22 In 4
cases
in
which the
deleted
chromosome
was
adequately studied by radioautography or by the new banding techniques, chromosome 13 was affected. In 2 of these cases the deletion involved an interstitial portion amounting to about a quarter of the long arm of Dn. D13 has two broad darkly staining bands in the mid to distal portion of the long arm with additional narrow dark bands 8. 9. 10. 11.
Galperin-Lemaître, H., Levi, S., Kirsch-Volders, M. Unpublished. Sandberg, A. A., Sakurai, M. Lancet, 1973, i, 375. Pierre, R. V., Hoagland, H. C. ibid. p. 1008. Allerdice, P. W., Davis, J. G., Klinger, H. P., et
al. Am. J. hum. Genet. 1969, 21, 499. 12. Gey, W. Humangenetik, 1970, 10, 362. 13. Grace, E., Drennan, J., Colver, D., Gordon, R. R. J. med. Genet. 1971, 8, 351. 14. Kahn, J., Reed, F. ibid. p. 372. 15. Laurent, C., Noel, B., David, M. Ann. Genet. 1971, 14, 33. 16. Lele, K. P., Penrose, L. S., Stallard, H. B. Ann. hum. Genet. 1963, 27, 171. 17. Orye, E., Delbeke, M. J., Vandenabelle, B. Lancet, 1971, ii, 1376. 18. Taylor, A. I. Humangenetik, 1970, 10, 209. 19. Thompson, H., Lyons, R. B. Hum. Chrom. Newsletter, 1965, 15, 21. 20. Wilson, M. G., Melnyk, J., Towner, J. W. J. med. Genet. 1969, 6, 322. 21. Wilson, M. G., Towner, J. W., Fujimoto, A. Am. J. hum. Genet. 1973, 25, 57. 22. Knudson, A. G. Proc. natn. Acad. Sci. U.S.A. 1971, 68, 820.
proximal and distal to these broad bands. The second distal broad band is deleted in the cases of Orye et al.17 and Wilson et a1.20,2l and is tentatively designated del (13) (q22::q32). Pruett and Catkins 23karyotyped 21 patients with retinoblastoma (17 sporadic, 4 bilateral) by standard techniques and were unable to show any chromosomal abnormality. Because of the devastating nature of this tumour, we chose to re-evaluate some of their patients using the newly developed trypsin banding technique of Seabright,24 in the hope of finding a consistent chromosomal-banding anomaly which might prove useful in prenatal diagnosis. Our patients included 7 with bilateral retinoblastomas (mother and daughter; mother, daughter, and son; two isolated bilateral tumours) and 5 with sporadic unilateral tumours. At least 5 cells with optimal banding
more
or more
were
studied in each
case.
None of the karyotypes of our patients showed a D-group deletion, the banding patterns being identical to those found in patients without retinoblastoma. Specifically, group-D chromosomes uniformly showed the presence of the major band on 13q which was reported as deleted in the two 13q cases noted above. A typical set of D-group chromosomes from one of our patients is shown in the figure. Technical variation in the number of visible bands
routinely occurs from metaphase to metaphase in any one preparation, presumably because of different conditions of chromosome contraction, and, furthermore, slight differences
of number and size of bands between
a
chromosome
pair in a given metaphase are the rule. Our patients had none of the major congenital malformations often found in Dq patients. Only one child in this study with bilateral tumour has moderate mental retardation and unusual facial and hand features. Review of additional metaphases from this patient failed to show a deletion or banding aberration.
Thus, these studies fail to demonstrate any abnormality of the bands on the D-group chromosomes in patients with bilateral retinoblastoma. It remains quite possible that most cases of retinoblastoma result from a single gene mutation on 13q while only some are caused by visible chromosomal aberrations there. Conversely, not all Dq patients develop retinoblastoma, and some probably involve not chromosome 13, but 14 or 15. Specific chromosome identification and banding in the Dq patients will be required to solve this uncertainty and to determine whether the same kind of deletion occurs in all 13q patients with retinoblastoma. Genetics Unit, Children’s Service, Massachusetts General Hospital, Harvard Medical School, Boston, Mass. 02114, U.S.A. 23. Pruett, R., Atkins, L. Archs Ophthal. 1969, 24. Seabright, M. Lancet, 1971, ii, 971.
R. LADDA L. ATKINS J. LITTLEFIELD R. PRUETT. 82, 177.