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47,XXX karyotype
Multiple Cancers in a Turner's Syndrome with 45,X/46,XXp -/46,XX/47,XXX Karyotype Hisako Ochi, Jin Takeuchi, and Avery A. Sandberg
ABSTRACT: A female patient with a clinical picture of Turner's syndrome had five separate malignant tumors (three squamous cell carcinomas of the tongue, a colon cancer, and a glioblastoma multiforme). Her peripheral blood cells showed a 45,X/46,XXp-/46,XX/47,XXX mosaicism. The findings are discussed in relation to other extragonadal tumors in Turner's syndrome reported to-date.
INTRODUCTION Extragonadal neoplasia in Turner's s y n d r o m e (TS) has been sporadically reported [1], however, m u l t i p l e cancers in TS have not been p u b l i s h e d yet. We report the clinical and cytogenetic findings of a female patient with TS who had six separate malignant tumors and whose karyotype was a 45,X/46,XXp-/46,XX/47,XXX mosaicism. CASE REPORT
The patient, a white housewife, was first seen at Roswell Park Memorial Institute (RPMI) in June 1960, at w h i c h time she was 43 years old and gave a history of primary amenorrhea, obesity (75 kg), and lack of breast development; she was of short stature (155 cm) and had a short neck. At that time, she was referred for consultation in the management of a leukoplakia on the right side of the tongue, w h i c h was first noted by the patient in December 1959. She had a tonsillectomy and a d e n o i d e c t o m y in 1929 and and a p p e n d e c t o m y in 1942. She had cysts of her scalp most of her life; and two of these were removed in 1959 because their location interferred with resting, and they were reported as benign. A cyst on the right lower leg was removed in June 1959, and though originally reported to be a basal cell carcinoma, it turned out to be an e p i d e r m o i d a l inclusion cyst with h y p e r p l a s i a u p o n review of the specimen. The patient gave no history of regular medications, including estrogens, and was not a smoker. The family history revealed diabetes mellitus in the patient's mother and in one of her siblings (different father); no familial history of cancer existed. Her father's
Roswell Park Memorial Institute, Buffalo,NY. Address requests for reprints to Dr. Avery A. Sandberg, Boswell Pork Memorial Institute, 666 Elm Street, Buffalo, N Y 14263. Received March 21, 1984; accepted August 14, 1984.
335 © 1985 Elsevier Science Publishing Co., Inc. 52 Vanderbilt Ave., New York, NY 10017
Cancer Genetics and Cytogenetics 16, 335-339 (1985) 0165-4608/85/$03.30
336
H. Ochi et al.
identity is ambiguous, and some of her relatives suspect that the patient may be the offspring of a s i s t e r - b r o t h e r relationship. In August 1961, the leukoplakic area began to increase in size, and rebiopsy showed a well-differentiated squamous cell carcinoma for w h i c h a right hemiglossectomy, h e m i m a n d i b u l e c t o m y , and right radical neck dissection were done in September 1961. However, 2 out of 70 right cervical l y m p h nodes were found to have meatastses. She did well until May 1962, when she d e v e l o p e d a swelling in the right s u b m a n d i b u l a r area that was revealed to be a recurrent squamous cell carcinoma. The patient was treated with focal radiation from June to July 1962 for a total of 5460 rads in 28 cycles. In October, the patient was found to have a carcinoma in the sigmoid colon for w h i c h she u n d e r w e n t an anterior sigmoid resection. The diagnosis was Duke's B1 glandular carcinoma in an a d e n o m a t o u s polyp, with invasion of the stalk. She was also noted to have m a n y colonic polyps; during the last 3 years, she had had annual colonoscopy, with adenomatous polyps being removed on each occasion. In July 1972, the patient was found to have a supraclavicular mass that was biopsied and s h o w n to be thyroid tissue. A thyroid scan showed d i m i n i s h e d uptake in the right lower pole, with the general thyroid 131I-uptake being w i t h i n normal limits. Exploration of the thyroid, biopsy of a pretracheal node, and biopsy of the right thyroid gland were negative for malignancy. In September 1981, the patient presented with a third malignancy, i.e., a p r i m a r y carcinoma of the left side of the tongue for w h i c h she u n d e r w e n t left partial glossectomy. The diagnosis was well-differentiated squamous cell carcinoma of the tongue with early invasion. In January 1983, the patient had an acute onset of expressive aphasia and was admitted to RPMI in February 1983. Computerized axial t o m o g r a p h y of the head showed possible metastases. She u n d e r w e n t craniotomy in March 1983, and a mass was detected at the parietooccipital region of the cerebrum. The diagnosis was glioblastoma multiforme. Postoperatively, she had a progressive course leading to death as a consequence of a pontine hemorrhage on A p r i l 18, 1983. An autopsy showed another primary carcinoma, i.e., squamous cell carcinoma "in situ" of the left side of the tongue. Thus, this patient had five separate malignant tumors. A u t o p s y also showed the absence of both ovaries, compatible with the diagnosis of ovarian agenesis (Turner's syndrome), and three a d e n o m a t o u s and one villaglandular p o l y p of the colon. The thyroid gland was unremarkable and no leukoplakia was found.
Table 1
Chromosome findings with G-banding
Number of metaphase
Karyotype
35 13 3 3 1
46,XX 46,X,del(X)(p22) 45,X 47,XXX 46,X,del(X)(p22),- 11 ,del(6)(p21), + der(11), t(11;?)(q25;?) 46,XX,dic(3;15)(p25;q24) 46,XX,t(1;21)(q21 ;q22) 46,XX,t(1 ;17)(q21;ql 1) 46,XX,t(8;15)(q24;q22) 46,XX,- 8, + 11
1 1 1 1 1
337
Multiple Cancers in Turner's Syndrome Mosaic
MATERIALS AND METHODS
The bone marrow cells obtained in June 1960 for cytogenetic analysis were examined by a direct method [2]. Metaphases were counted, but due to the somewhat poor quality of the preparations, were not analyzed. A second cytogenetic analysis was performed on the peripheral blood cells obtained in March 1983. The buffy coat was incubated for 48 hr in RPMI 1640 medium supplemented with 16.7% fetal bovine serum and 0.15 mg/ml of reconstituted phytohemagglutinin (Wellcome) medium. Colcemid was added at a concentration of 0.05 vLg/ml, 1 hour before harvest. The trypsin-Giemsa banding method was used for analysis of the karyotypes. The cytogenetic analysis of the skin fibroblasts could not be done because of the deterioration of the patient's condition. RESULTS
The first cytogenetic analysis (June 1960) revealed 34 of 37 mitoses to have 46 chromosomes, 1 with 45 chromosomes, and 2 with 44. The second cytogenetic analysis (March 1983) showed 35 out of 60 banded metaphases to be normal diploid 46,XX. However, three clonal X-chromosome abnormalities were also present, i.e., X monosomy (Fig. 1A), Xp deletion of band p22 (Fig. 1B), and X trisomy (Fig. 1D), which were found in 14, 3, and 3 metaphases, respectively (Table 1). Other metaphases showed nonclonal abnormalities. DISCUSSION
Cytogenetic studies of Turner's syndrome (TS) have disclosed that the classical 45,X karyotype is only found in about 60% of the patients and an isochromosome Xq and 45,X/46,XX mosaicism in 20% and 10% of patients with this syndrome, respectively [3, 4]. However, as far as we know, there have been no reports of TS with 45,X/46,XXp-/46,XX/47,XXX mosaicism. Our patient showed primary amenorrhea with gonadal agenesis, short stature, and a short neck. Besides the characteristic clinical picture of TS, she was also found to have 45,X and 45,XXp- clones in her peripheral blood cells accompanying the 46XX (normal) and 47,XXX clones. The first cytogenetic study, which was done in June 1960, also revealed hypodiploid cells in her bone marrow cells, though these cells could not be identified as a clone at that time due to the poor quality of the preparations. Despite the low frequency of the responsible karyotypes (45,X and 46,XXp-) in her peripheral blood cells, the patient showed a typical
Figure 1
X-chromosomes from cells with (A) 45,X; (B) 46,X,del(X)(p22); (C} 46,XX; and (D)
47,XXX.
a
b
c
d
338
u. Ochi et al.
p h e n o t y p e of TS. This fact is not surprising, as there is no correlation between the relative n u m b e r of various cell types of the tissues involved and the ultimate phenotypic expression [5]. However, an interpretation of which karyotype is responsible for the i n d i v i d u a l p h e n o t y p e expression is very difficult because of mosaicism. The risk for neoplastic disease is increased in patients with certain congenital chromosome abnormalities, e.g., Down's syndrome, 1 3 q - syndrome, and Klinefelter's s y n d r o m e [6]. In Turner's syndrome, a t e n d e n c y for developing neurogenic tumors has been suggested [7]; our patient suffered from a glioblastoma multiforme at the age of 65. This may be supportive for the abo.ve hypothesis; however, all neurogenic tumors reported in TS [6, 7] have been found before the age of 40. Interestingly, two TS patients were found to have adenocarcinomas in sigmoid polyps at ages 38 and 44, respectively [7], findings similar to those of our patient who was diagnosed to have the same disease at age 46. No squamous cell carcinoma of the tongue in TS patients has been reported. The relationship between the five tumors and TS in our patient is obscure m a i n l y because we did not have the o p p o r t u n i t y to examine the chromosomes of these tumors. A 50-year-old w o m a n with TS and a mosaic c h r o m o s o m e constitution (45,X/46,XX) was reported to have chronic myelogenous l e u k e m i a at age 50; her leukemic cells had the karyotype of 45,X,Ph 1+ , and the authors suggested that the c h r o m o s o m a l l y abnormal clone was more prone to undergo neoplastic transformation than the cytogenetically normal cells [8]. If it is true, and all the tumors of our patients were derived from cells with 45,X or 4 6 , X X p - , the occurrence of m u l t i p l e cancers in our patient w o u l d be partly explained. Our patient had m a n y a d e n o m a t o u s polyps in the colon, m u l t i p l e cysts of the skin, and a glioblastoma, along with other tumors. Such a clinical picture m a y be compatible with the diagnosis of Gardner's syndrome, w h i c h consists of m u l t i p l e osteomas, fibromas, lipomas, fibrosarcomas, epideral inclusion cysts, and leiomyomas that are associated with intestinal p o l y p o s i s occurring exclusively in the colon and rectum [9], or with Turcot's syndrome, w h i c h is the association of malignant tumors of the central nervous system with familial p o l y p o s i s of the colon [10]. Both syndromes are hereditary disorders, and the m o d e of inheritance is a u t o s o m a l l y dominant in Gardner's s y n d r o m e and autosomally recessive or d o m i n a n t in Turcot's s y n d r o m e [11]. Because of our failure to obtain a complete familial pedigree, we could not establish w h e t h e r our patient's disease was an inherited one. A c o m m o n cause of carcinoma of the m o u t h is tobacco smoking [9]; some skin diseases, e.g., xeroderma pigmentosa, Darier's disease, and Bowen's disease, are k n o w n to be associated with a high incidence of skin cancer or systemic cancer [9]. However, we could not establish any positive evidence for these diseases in our patient; she denied habitual smoking. Some chemicals or drugs may cause a variety of cancers, however, our patient gave no history of drug or chemical exposure. She was treated with focal irradiation (5460 rads) in 1962, but had not received any chemotherapy. This radiation might be related to the d e v e l o p m e n t of some of her subsequent cancers, though no definitive evidence can be presented. Thus, the etiologic relationship between the constitutional chromosome abnormalities and the various cancers in our patient will r e m a i n unclear until more cases with similar findings are studied. We wish to thank Dr. Lemuel Herrera-Ornelas, Kathleen F. Carr, and Richard P. Paczynski for their help. Supported in part by Grant CA-28853 from the National Cancer Institute.
M u l t i p l e Cancers in T u r n e r ' s S y n d r o m e M o s a i c
339
REFERENCES 1. Sandberg AA (1983): The X chromosome in human neoplasia, including sex chromatin and congenital conditions with X-chromosome anomalies. In: Cytogenetics of the Mammalian X Chromosome, Part B, A.A. Sandberg, ed., Alan R. Liss, New York, pp 459-498. 2. Sandberg AA, Koepf GF, Crosswhite LH, Hauschka TS (1960): The chromosome constitution of human marrow in various developmental and blood disorders. Am J Hum Genet 12:231-249. 3. Thompson JS, Thompson MW (1980): Genetics in Medicine, ed 3, W.B. Saunders, Philadelphia, pp 176-177. 4. Fryns JP, Kleczkowska A, Van Den Berghe H (1983): The X chromosome and sexual development: Clinical aspects. In: Cytogenetics of the Mammalian X Chromosome. Part B, A.A. Sandberg, ed., Alan R. Liss, New York, pp 115-126. 5. Shapiro LR (1983): Phenotypic expressions of numeric and structural X-chromosome abnormalities. In: Cytogenetics of the Mammalian X Chromosome, Part B, A.A., Sandberg, ed., Alan R. Liss, New York, pp 321-339. 6. Sandberg AA (1980): The Chromosomes in Human Cancer and Leukemia, Elsevier NorthHolland, New York, pp 776. 7. Wertelecki W, Fraumeni JF, Mulvihill JJ (1970): Nongonadal neoplasia in Turner's syndrome. Cancer 26:485-488. 8. Chaganti RSK, Bailey RB, Jhanwar, SC, Arlin ZA, Clarkson BD (1982): Chronic myelogenous leukemia in the monosomic cell line of a fertile Turner syndrome mosaic (45,X/ 46,XX). Cancer Genet Cytogenet 5:215-221. 9. Domonkos AN (1971): Andrew's Disease of the Skin, ed 6, W.B. Saunders, Philadelphia. 10. Spiro HM (1983): Clinical Gastroenterology, ed 3, Macmillan, New York, pp 996. 11. McKusick, VA (1983): Mendelian Inheritance in Man. Catalogs of Autosomal Dominant, Autosomal Recessive and X-Linked Phenotypes, ed 6, Johns Hopkins University Press, Baltimore.
ABSTRACT: A female patient with a clinical picture of Turner's syndrome had five separate malignant tumors (three squamous cell carcinomas of the tongue, a colon cancer, and a glioblastoma multiforme). Her peripheral blood cells showed a 45,X/46,XXp-/46,XX/47,XXX mosaicism. The findings are discussed in relation to other extragonadal tumors in Turner's syndrome reported to-date.
INTRODUCTION Extragonadal neoplasia in Turner's s y n d r o m e (TS) has been sporadically reported [1], however, m u l t i p l e cancers in TS have not been p u b l i s h e d yet. We report the clinical and cytogenetic findings of a female patient with TS who had six separate malignant tumors and whose karyotype was a 45,X/46,XXp-/46,XX/47,XXX mosaicism. CASE REPORT
The patient, a white housewife, was first seen at Roswell Park Memorial Institute (RPMI) in June 1960, at w h i c h time she was 43 years old and gave a history of primary amenorrhea, obesity (75 kg), and lack of breast development; she was of short stature (155 cm) and had a short neck. At that time, she was referred for consultation in the management of a leukoplakia on the right side of the tongue, w h i c h was first noted by the patient in December 1959. She had a tonsillectomy and a d e n o i d e c t o m y in 1929 and and a p p e n d e c t o m y in 1942. She had cysts of her scalp most of her life; and two of these were removed in 1959 because their location interferred with resting, and they were reported as benign. A cyst on the right lower leg was removed in June 1959, and though originally reported to be a basal cell carcinoma, it turned out to be an e p i d e r m o i d a l inclusion cyst with h y p e r p l a s i a u p o n review of the specimen. The patient gave no history of regular medications, including estrogens, and was not a smoker. The family history revealed diabetes mellitus in the patient's mother and in one of her siblings (different father); no familial history of cancer existed. Her father's
Roswell Park Memorial Institute, Buffalo,NY. Address requests for reprints to Dr. Avery A. Sandberg, Boswell Pork Memorial Institute, 666 Elm Street, Buffalo, N Y 14263. Received March 21, 1984; accepted August 14, 1984.
335 © 1985 Elsevier Science Publishing Co., Inc. 52 Vanderbilt Ave., New York, NY 10017
Cancer Genetics and Cytogenetics 16, 335-339 (1985) 0165-4608/85/$03.30
336
H. Ochi et al.
identity is ambiguous, and some of her relatives suspect that the patient may be the offspring of a s i s t e r - b r o t h e r relationship. In August 1961, the leukoplakic area began to increase in size, and rebiopsy showed a well-differentiated squamous cell carcinoma for w h i c h a right hemiglossectomy, h e m i m a n d i b u l e c t o m y , and right radical neck dissection were done in September 1961. However, 2 out of 70 right cervical l y m p h nodes were found to have meatastses. She did well until May 1962, when she d e v e l o p e d a swelling in the right s u b m a n d i b u l a r area that was revealed to be a recurrent squamous cell carcinoma. The patient was treated with focal radiation from June to July 1962 for a total of 5460 rads in 28 cycles. In October, the patient was found to have a carcinoma in the sigmoid colon for w h i c h she u n d e r w e n t an anterior sigmoid resection. The diagnosis was Duke's B1 glandular carcinoma in an a d e n o m a t o u s polyp, with invasion of the stalk. She was also noted to have m a n y colonic polyps; during the last 3 years, she had had annual colonoscopy, with adenomatous polyps being removed on each occasion. In July 1972, the patient was found to have a supraclavicular mass that was biopsied and s h o w n to be thyroid tissue. A thyroid scan showed d i m i n i s h e d uptake in the right lower pole, with the general thyroid 131I-uptake being w i t h i n normal limits. Exploration of the thyroid, biopsy of a pretracheal node, and biopsy of the right thyroid gland were negative for malignancy. In September 1981, the patient presented with a third malignancy, i.e., a p r i m a r y carcinoma of the left side of the tongue for w h i c h she u n d e r w e n t left partial glossectomy. The diagnosis was well-differentiated squamous cell carcinoma of the tongue with early invasion. In January 1983, the patient had an acute onset of expressive aphasia and was admitted to RPMI in February 1983. Computerized axial t o m o g r a p h y of the head showed possible metastases. She u n d e r w e n t craniotomy in March 1983, and a mass was detected at the parietooccipital region of the cerebrum. The diagnosis was glioblastoma multiforme. Postoperatively, she had a progressive course leading to death as a consequence of a pontine hemorrhage on A p r i l 18, 1983. An autopsy showed another primary carcinoma, i.e., squamous cell carcinoma "in situ" of the left side of the tongue. Thus, this patient had five separate malignant tumors. A u t o p s y also showed the absence of both ovaries, compatible with the diagnosis of ovarian agenesis (Turner's syndrome), and three a d e n o m a t o u s and one villaglandular p o l y p of the colon. The thyroid gland was unremarkable and no leukoplakia was found.
Table 1
Chromosome findings with G-banding
Number of metaphase
Karyotype
35 13 3 3 1
46,XX 46,X,del(X)(p22) 45,X 47,XXX 46,X,del(X)(p22),- 11 ,del(6)(p21), + der(11), t(11;?)(q25;?) 46,XX,dic(3;15)(p25;q24) 46,XX,t(1;21)(q21 ;q22) 46,XX,t(1 ;17)(q21;ql 1) 46,XX,t(8;15)(q24;q22) 46,XX,- 8, + 11
1 1 1 1 1
337
Multiple Cancers in Turner's Syndrome Mosaic
MATERIALS AND METHODS
The bone marrow cells obtained in June 1960 for cytogenetic analysis were examined by a direct method [2]. Metaphases were counted, but due to the somewhat poor quality of the preparations, were not analyzed. A second cytogenetic analysis was performed on the peripheral blood cells obtained in March 1983. The buffy coat was incubated for 48 hr in RPMI 1640 medium supplemented with 16.7% fetal bovine serum and 0.15 mg/ml of reconstituted phytohemagglutinin (Wellcome) medium. Colcemid was added at a concentration of 0.05 vLg/ml, 1 hour before harvest. The trypsin-Giemsa banding method was used for analysis of the karyotypes. The cytogenetic analysis of the skin fibroblasts could not be done because of the deterioration of the patient's condition. RESULTS
The first cytogenetic analysis (June 1960) revealed 34 of 37 mitoses to have 46 chromosomes, 1 with 45 chromosomes, and 2 with 44. The second cytogenetic analysis (March 1983) showed 35 out of 60 banded metaphases to be normal diploid 46,XX. However, three clonal X-chromosome abnormalities were also present, i.e., X monosomy (Fig. 1A), Xp deletion of band p22 (Fig. 1B), and X trisomy (Fig. 1D), which were found in 14, 3, and 3 metaphases, respectively (Table 1). Other metaphases showed nonclonal abnormalities. DISCUSSION
Cytogenetic studies of Turner's syndrome (TS) have disclosed that the classical 45,X karyotype is only found in about 60% of the patients and an isochromosome Xq and 45,X/46,XX mosaicism in 20% and 10% of patients with this syndrome, respectively [3, 4]. However, as far as we know, there have been no reports of TS with 45,X/46,XXp-/46,XX/47,XXX mosaicism. Our patient showed primary amenorrhea with gonadal agenesis, short stature, and a short neck. Besides the characteristic clinical picture of TS, she was also found to have 45,X and 45,XXp- clones in her peripheral blood cells accompanying the 46XX (normal) and 47,XXX clones. The first cytogenetic study, which was done in June 1960, also revealed hypodiploid cells in her bone marrow cells, though these cells could not be identified as a clone at that time due to the poor quality of the preparations. Despite the low frequency of the responsible karyotypes (45,X and 46,XXp-) in her peripheral blood cells, the patient showed a typical
Figure 1
X-chromosomes from cells with (A) 45,X; (B) 46,X,del(X)(p22); (C} 46,XX; and (D)
47,XXX.
a
b
c
d
338
u. Ochi et al.
p h e n o t y p e of TS. This fact is not surprising, as there is no correlation between the relative n u m b e r of various cell types of the tissues involved and the ultimate phenotypic expression [5]. However, an interpretation of which karyotype is responsible for the i n d i v i d u a l p h e n o t y p e expression is very difficult because of mosaicism. The risk for neoplastic disease is increased in patients with certain congenital chromosome abnormalities, e.g., Down's syndrome, 1 3 q - syndrome, and Klinefelter's s y n d r o m e [6]. In Turner's syndrome, a t e n d e n c y for developing neurogenic tumors has been suggested [7]; our patient suffered from a glioblastoma multiforme at the age of 65. This may be supportive for the abo.ve hypothesis; however, all neurogenic tumors reported in TS [6, 7] have been found before the age of 40. Interestingly, two TS patients were found to have adenocarcinomas in sigmoid polyps at ages 38 and 44, respectively [7], findings similar to those of our patient who was diagnosed to have the same disease at age 46. No squamous cell carcinoma of the tongue in TS patients has been reported. The relationship between the five tumors and TS in our patient is obscure m a i n l y because we did not have the o p p o r t u n i t y to examine the chromosomes of these tumors. A 50-year-old w o m a n with TS and a mosaic c h r o m o s o m e constitution (45,X/46,XX) was reported to have chronic myelogenous l e u k e m i a at age 50; her leukemic cells had the karyotype of 45,X,Ph 1+ , and the authors suggested that the c h r o m o s o m a l l y abnormal clone was more prone to undergo neoplastic transformation than the cytogenetically normal cells [8]. If it is true, and all the tumors of our patients were derived from cells with 45,X or 4 6 , X X p - , the occurrence of m u l t i p l e cancers in our patient w o u l d be partly explained. Our patient had m a n y a d e n o m a t o u s polyps in the colon, m u l t i p l e cysts of the skin, and a glioblastoma, along with other tumors. Such a clinical picture m a y be compatible with the diagnosis of Gardner's syndrome, w h i c h consists of m u l t i p l e osteomas, fibromas, lipomas, fibrosarcomas, epideral inclusion cysts, and leiomyomas that are associated with intestinal p o l y p o s i s occurring exclusively in the colon and rectum [9], or with Turcot's syndrome, w h i c h is the association of malignant tumors of the central nervous system with familial p o l y p o s i s of the colon [10]. Both syndromes are hereditary disorders, and the m o d e of inheritance is a u t o s o m a l l y dominant in Gardner's s y n d r o m e and autosomally recessive or d o m i n a n t in Turcot's s y n d r o m e [11]. Because of our failure to obtain a complete familial pedigree, we could not establish w h e t h e r our patient's disease was an inherited one. A c o m m o n cause of carcinoma of the m o u t h is tobacco smoking [9]; some skin diseases, e.g., xeroderma pigmentosa, Darier's disease, and Bowen's disease, are k n o w n to be associated with a high incidence of skin cancer or systemic cancer [9]. However, we could not establish any positive evidence for these diseases in our patient; she denied habitual smoking. Some chemicals or drugs may cause a variety of cancers, however, our patient gave no history of drug or chemical exposure. She was treated with focal irradiation (5460 rads) in 1962, but had not received any chemotherapy. This radiation might be related to the d e v e l o p m e n t of some of her subsequent cancers, though no definitive evidence can be presented. Thus, the etiologic relationship between the constitutional chromosome abnormalities and the various cancers in our patient will r e m a i n unclear until more cases with similar findings are studied. We wish to thank Dr. Lemuel Herrera-Ornelas, Kathleen F. Carr, and Richard P. Paczynski for their help. Supported in part by Grant CA-28853 from the National Cancer Institute.
M u l t i p l e Cancers in T u r n e r ' s S y n d r o m e M o s a i c
339
REFERENCES 1. Sandberg AA (1983): The X chromosome in human neoplasia, including sex chromatin and congenital conditions with X-chromosome anomalies. In: Cytogenetics of the Mammalian X Chromosome, Part B, A.A. Sandberg, ed., Alan R. Liss, New York, pp 459-498. 2. Sandberg AA, Koepf GF, Crosswhite LH, Hauschka TS (1960): The chromosome constitution of human marrow in various developmental and blood disorders. Am J Hum Genet 12:231-249. 3. Thompson JS, Thompson MW (1980): Genetics in Medicine, ed 3, W.B. Saunders, Philadelphia, pp 176-177. 4. Fryns JP, Kleczkowska A, Van Den Berghe H (1983): The X chromosome and sexual development: Clinical aspects. In: Cytogenetics of the Mammalian X Chromosome. Part B, A.A. Sandberg, ed., Alan R. Liss, New York, pp 115-126. 5. Shapiro LR (1983): Phenotypic expressions of numeric and structural X-chromosome abnormalities. In: Cytogenetics of the Mammalian X Chromosome, Part B, A.A., Sandberg, ed., Alan R. Liss, New York, pp 321-339. 6. Sandberg AA (1980): The Chromosomes in Human Cancer and Leukemia, Elsevier NorthHolland, New York, pp 776. 7. Wertelecki W, Fraumeni JF, Mulvihill JJ (1970): Nongonadal neoplasia in Turner's syndrome. Cancer 26:485-488. 8. Chaganti RSK, Bailey RB, Jhanwar, SC, Arlin ZA, Clarkson BD (1982): Chronic myelogenous leukemia in the monosomic cell line of a fertile Turner syndrome mosaic (45,X/ 46,XX). Cancer Genet Cytogenet 5:215-221. 9. Domonkos AN (1971): Andrew's Disease of the Skin, ed 6, W.B. Saunders, Philadelphia. 10. Spiro HM (1983): Clinical Gastroenterology, ed 3, Macmillan, New York, pp 996. 11. McKusick, VA (1983): Mendelian Inheritance in Man. Catalogs of Autosomal Dominant, Autosomal Recessive and X-Linked Phenotypes, ed 6, Johns Hopkins University Press, Baltimore.