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ORIGINAL ARTICLE
Year : 2001  |  Volume : 49  |  Issue : 1  |  Page : 37-42

Genetic profile of 81 retinoblastoma patients from a referral hospital in Southern India


1 MS (MLT). Department of Genetics and Molecular Biology, Vision Reasearch Foundation, Chennai, India
2 MS (MLT). Department of Genetics and Molecular Biology, Vision Research Foundation, Chennai, India
3 MBBS, DO. Department of Genetics and Molecular Biology, Vision Research Foundation, Chennai, India
4 BSc, PGDMLT. Department of Genetics and Molecular Biology, Vision Research Foundation, Chennai, India
5 MD. Department of Genetics and Molecular Biology, Vision Research Foundation, Chennai, India

Correspondence Address:
Rajasekhar Harini
MS (MLT). Department of Genetics and Molecular Biology, Vision Reasearch Foundation, Chennai, India

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Source of Support: None, Conflict of Interest: None


PMID: 15887714

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  Abstract 

Purpose: To determine chromosomal abnormalities and inheritance pattern in patients with retinoblastoma from a referral hospital in southern India.
Materials and Methods: Eighty-one retinoblastoma patients from 78 families were included in this study. Peripheral venous blood was taken for chromosomal analysis and pedigree was ascertained for segregation analysis.
Results: Male to female ratio was 1.7:1, 55.56% were bilateral retinoblastoma, the mean age of onset was 12.37 months in bilateral and 33.07 months in unilateral cases (p=0.048). Majority (90.12%) had sporadic inheritance and 6.17% had autosomal dominant inheritance. In chromosomal abnormalities, 8.33% had 13q14 deletion, three cases had de novo balanced translocations.
Conclusion: The age of onset of the disease was much earlier in the bilateral cases compared to unilateral cases. Sporadic inheritance was predominant while only a small percentage of patients had autosomal dominant inheritance. The percentage of patients with 13q14 deletion was higher than reported in the literature and three novel chromosomal translocations were observed. This is one of the largest series of cases reported from India.

Keywords: Retinoblastoma, autosomal dominant, chromosomal abnormalities, segregation analysis.


How to cite this article:
Harini R, Ata-ur-Rasheed M, Shanmugam MP, Amali J, Das D, Kumaramanickavel G. Genetic profile of 81 retinoblastoma patients from a referral hospital in Southern India. Indian J Ophthalmol 2001;49:37-42

How to cite this URL:
Harini R, Ata-ur-Rasheed M, Shanmugam MP, Amali J, Das D, Kumaramanickavel G. Genetic profile of 81 retinoblastoma patients from a referral hospital in Southern India. Indian J Ophthalmol [serial online] 2001 [cited 2024 Mar 28];49:37-42. Available from: https://journals.lww.com/ijo/pages/default.aspx/text.asp?2001/49/1/37/22662

Retinoblastoma is the most common malignant intraocular tumour in the paediatric age group[1] with an incidence of 1:12000 to 1:23000 live births amongst different races.[2-7] The tumour in retinoblastoma arises from the retinal precursor cells[8] and therefore manifests as unilateral or bilateral tumour. If the pineal body is involved it is called trilateral retinoblastoma. [9,10] Retinoblastoma can develop as a result of a somatic or germinal mutation, but the susceptibility to the disease is inherited in an autosomal dominant manner. Knudson's "Two Hit Hypothesis" provides an explanation for the genetic basis of two forms of retinoblastoma:[11-13] (i) the heritable, which is bilateral and multifocal, and (ii) the non-heritable, which is unilateral and unifocal. Stallard gave the first clue to the location of retinoblastoma gene in 1962.[14] High-resolution banding localised the retinoblastoma gene to sub-band 13q14.11. [15,16] The RBI gene expressed in a majority of cells has been well characterised as a tumour suppressor gene and both alleles must be inactivated or lost for tumourigenesis. [1,17-21] Only 5-6% of patients with retinoblastoma have cytogenetic deletions; [1,2] the remaining 95% of the mutations occurring in the retinoblastoma gene are submicroscopic. [1,2] In therapeutic experiments transgenic mice and gene therapy methods have been attempted to find a cure for retinoblastoma.[22]

In the present study, conducted at a referral hospital in southern India, we propose to (i) determine the mode of inheritance and (ii) detect the cytogenetic aberrations in these 81 retinoblastoma patients.


  Materials and Methods Top


Retinoblastoma patients were referred to the Department of Genetics & Molecular Biology, Vision Research Foundation, Sankara Nethralaya, Chennai, where pedigree was drawn and analysed before counselling. Information obtained in this study included parental consanguinity, age of onset of retinoblastoma, family history, gender distribution and laterality. Autosomal dominant inheritance is labelled when one parent has retinoblastoma and 50% of children of either gender are affected with the same disease. Sporadic inheritance is labelled when no other family member is affected with retinoblastoma. Blood was collected from the affected individuals for chromosomal analysis. Statistical and cytogenetic analyses were done.


  Statistical analysis Top


To confirm whether all these families showed an autosomal dominant mode of inheritance, Neel and Schull segregation analysis[23] was used as follows:

where, O = observed and E = expected.


  Cytogenetic analysis Top


Lymphocyte culture[24] was set with 0.4 ml of peripheral blood added to 10ml of RPMI medium (0.0103 mg / ml, Hi-media, India) containing 20% foetal calf serum (Hi-media, India), 6 mg L-glutamine (Hi-media, India), 2 mg penicillin (Hi-media, India) and 0.1 ml of the mitogen phytohemagglutinin (GibcoBRL,USA). After incubation at 37°C for 72 hours, 50 μl of methotrexate (4.5 x 10-6 mg/μl, Sigma, USA) was added and incubated at 37°C for 17 hours. The mixture was centrifuged at 1500 rpm for 10 minutes. The cells were washed twice with fresh unsupplemented medium and centrifuged again. Subsequently 50 μl of thymidine solution (2.5 x 10-4 mg/μl, Sigma, USA) was added to 10ml of the medium and incubated at 37°C for 5-6 hours. Finally, 10μl of colchicine (2 x 10-4 mg / μl, Sigma, USA) was added 10 minutes before harvesting the cells. The cells were fixed in methanol: acetic acid (3:1) and then the slides were prepared and stained using GTG-banding. Parents of 9 patients, however, refused cytogenetic study.


  Results Top


In the three and a half years between September 1995 and March 1999, we examined 81 patients from 78 retinoblastoma families referred from all over India. These included 51 males (62.96%) and 30 females (37.04%) (male to female ratio = 1.7:1); the age of onset of the disease according to the history ranged from 1 month to 24 years. Forty-five patients had bilateral manifestations (55.56%), while 36 had unilateral (44.44%). The mean age of onset for bilateral cases was 12.37 months (range = 10 days to 48 months, median = 6.5 months) whereas in the unilateral cases, it was nearly three times higher - 33.07 months (range = 1 to 288 months, median = 22.5 months). Age of onset of the disease differed significantly between unilateral and bilateral groups [Figure - 1] with a 'p' value of 0.048. In the groups put together, the mean age of onset was 21.56 months (range = 10 days to 288 months, median = 12 months).

Only 5 families (8 patients) had positive family history for the disease (6.41%) (see pedigrees shown in [Figure - 2]). The inheritance pattern was sporadic in 73 (90.12%), autosomal dominant (ad) in 5 (6.17%) and suspected ad in 3 (3.7%) patients. Nearly half, 36 out of 78 (46.15%) families were one-child families. There were 7 (8.97%) consanguineous marriages amongst the 78 families. On segregation analysis the x2 was 16.536, the value of x2 is significant with one degree of freedom if it is greater than 3.841 and therefore there was no significant departure from the expected number of normal and affected offspring assuming autosomal dominant inheritance. Six of 72 patients (8.33%) had 13q14 deletion. Two patients (2.78%) had 1q41 chromatid break. Three (4.33%) de novo balanced translocations, t(6:11) (q13:q25) [Figure - 3], t(12:13) (q23:q33) and t(13:4) (q14:p16.3) were observed in three unrelated in three unrelated patients; all were mosaic with a normal choromosomal constitution as well.


  Discussion Top


In India, retinoblastoma is the leading paediatric tumour after Wilm's tumour and lymphoma, [25,26] and stands third in the five-year survival rate next to thyroid carcinoma and Hodgkin's disease.[27] In a northern Indian study[28] unilateral disease was 61.8%, median age at presentation was 12 months for bilateral and 41 months for unilateral retinoblastoma; male / female ratio was 1.41:1; consanguinity was 17% and positive family history was 1.7%. In our study, unilateral disease was 44.44%, median age of onset was 12.37 months for bilateral and 33.07 months for unilateral retinoblastoma; male/female ratio was 1.7:1; consanguinity was 8.97% and positive family history was present in 6.41% of families. We believe that the reason for the preponderance of males in this ad disease could be due to cultural and social influences.

In a majority of retinoblastoma cases, the symptoms become evident before the age of three.[29] It was similar in our patients (mean age of onset: 21.56 months). It has been reported that the mean age for bilateral cases is 12 months whereas in unilateral cases it is 23 months.[30] In our study the average age of onset for bilateral cases was 12.37 months and for unilateral cases, 33.07 months. The higher age of onset in the unilateral group was due to the fact that two patients in our series reported unilateral retinoblastoma after 20 years of age. Cases of late onset of retinoblastoma however have been reported earlier. [31,32]

A majority of the patients (90.12%) in our study showed sporadic inheritance. Five individuals of two unrelated families showed autosomal dominant inheritance. However, in three unrelated individuals it could possibly be an autosomal dominant inheritance; particularly, in one family where a second cousin was affected. We presume this family could have low penetrance of the retinoblastoma gene as reported earlier. [33,34] Even though majority of cases were sporadic, segregation analysis showed autosomal dominant inheritance. This statistical correlation was possibly because nearly half of the families (46.15%) had only one child.

The consanguinity observed in these families could be due to the high incidence of consanguineous marriages in our population[35] and therefore could be coincidental. The reported incidence of 13q14 deletion has been from 4 to 5%. [15, 16, 36-38] In our study it was 8.33% considerably higher than these reports. Potluri et al[39] reported non-random chromosomal aberrations in 82 patients, where they observed monosomies and deletions of chromosome 13 in a few cases and additional copies of 1q, 6p or extra chromosome 6 in a few others. We observed three (4.33%) de novo autosomal balanced translocations, t(6:11) (q13:q25), t(12:13) (q23:q33) and t(13:4) (q14:p16.3). The first was a male but the other two were females. Interestingly, all three patients were mosaics with normal cells as well and such mosaicism has been reported earlier[40] both in 13q14 deletions[41] and in balanced translocations. [42,43] Autosomal de novo balanced translocations reported were t(1:13) (p22:q12)[44] t(13:18) (q14.1:q12.2)[45] and t(2:13) (p24.3:q14.2).[40] Only further molecular genetic studies could prove whether the translocation case we report with non-involvement of chromosome 13[t(6:11)] could be coincidental or not. Rosenberg et al applied flourescent-in-situ-hybridisation (FISH) to study a constitutive rearrangement involving chromosomes 4 and 13. This technique helps to detect translocations and micro-deletions easily.[46] We also had two patients with chromatid break in 1q41 region; deletion 1q41\?\ter has been reported earlier.[47]

In our study, except for one 1q41 chromatid break, all other patients with a cytogenetic abnormality had bilateral retinoblastoma. Patients with bilateral retinoblastoma have an increased incidence of second primary tumours and this rate is further increased in those treated with external radiotherapy.[48] Our study period was too short to assess for any second primary tumours. The 13q14 region has been shown to harbour the osteosarcoma gene as well,[49] however, recently this region has generated considerable interest and shown to harbour genes for prostate, pituitary, breast and bladder cancers too.[50-53] In the west, molecular genetic techniques like FISH, DNA fragment analysis, and mutational screening are presently being used in the diagnosis and genetic counselling for patients and families with retinoblastoma. This could in time be made safer and cheaper than conventional ophthalmic screening.[54-[61] Currently molecular genetic studies are in progress in these patients; such methods could help one-child families to have normal children.

In conclusion, in the 81 retinoblastoma patients we found: (i) earlier onset (mean age of onset: 12.37 months) of the disease in bilateral retinoblastoma cases than unilateral (mean age of onset: 33.07 months), (ii) higher incidence of 13q14 chromosomal deletion (8.33%) than in earlier reports, (iii) sporadic inheritance of the disease in a majority of the patients (90.12%) and (iv) three novel de novo balanced translocations.



 
  References Top

1.
Murphree AL. Molecular genetics of retinoblastoma. Ophthal Clin North Am 1995;8:155-66.  Back to cited text no. 1
    
2.
Gallie BL, Dunn JM, Chan HSL, Hamel PA, Phillips RA. The Genetics of Retinoblastoma. Pediatr Clin North Am 1991;38:299-315.  Back to cited text no. 2
    
3.
Al-Idrissi I, Al-Kaff A, Senft SH. Cumulative incidence of retinoblastoma in Riyadh, Saudi Arabia. Ophthalmic Pediatr Genet 1992;13:9-12.  Back to cited text no. 3
    
4.
DerKinderen DJ, Koten JW, Tan KEWP, Beemer FA, Van Romunde LKJ, Den Otter W. Parental age in sporadic hereditary retinoblastoma. Am J Ophthalmol 1990;110:605-09.  Back to cited text no. 4
    
5.
Tamboli A, Podgor MJ, Horm JW. The incidence of retinoblastoma in the United States: 1974 through 1985. Arch Ophthalmol 1990;108:128-32.  Back to cited text no. 5
[PUBMED]  [FULLTEXT]  
6.
The Committee for the National Registry of Retinoblastoma. Survival rate and risk factors for patients with retinoblastoma in Japan. Jpn J Ophthalmol 1992;36:121-31.  Back to cited text no. 6
[PUBMED]  [FULLTEXT]  
7.
Sanders BM, Draper GJ, Kingston JE. Retinoblastoma in Great Britain 1969-1980: incidence, treatment, and survival. Br J Ophthalmol 1988;72:576-83.  Back to cited text no. 7
[PUBMED]  [FULLTEXT]  
8.
Nork TM, Schwartz TL., Doshi HM., Millecchia LL. Retinoblastoma cell of origin. Arch Ophthalmol 1995;113:791-802.  Back to cited text no. 8
    
9.
Pesin SR, Shields JA. Seven cases of trilateral retinoblastoma. Am J Ophthalmol 1989;107:121-126.  Back to cited text no. 9
[PUBMED]  [FULLTEXT]  
10.
Bader JL, Meadows AT, Zimmerman LE, Rorke LB, Voute PA, Champion LA, Miller RW. Bilateral retinoblastoma and ectopic intracranial retinoblastoma. Trilateral retinoblastoma. Cancer Genet Cytogenet 1982;5(3):203-13.  Back to cited text no. 10
    
11.
Kundson AG. Mutation of cancer. Statistical study of retinoblastoma. Proc Natl Acad Sci 1971;68:820-23.  Back to cited text no. 11
    
12.
Godbout R, Dryja TP, Squire J, Gallie BL, Phillips RA. Somatic inactivation of genes on chromosome 13 is a common event in retinoblastoma. Nature 1983;304:451-53.  Back to cited text no. 12
[PUBMED]  [FULLTEXT]  
13.
Harbour JW. Tumor suppressor genes in ophthalmology. Surv Ophthalmol 1999;44:3:235-46.  Back to cited text no. 13
[PUBMED]  [FULLTEXT]  
14.
Stallard HB. The conservative treatment of retinoblastoma. Doyne memorial lecture Trans Ophthal Soc UK 1962;82:473-34.  Back to cited text no. 14
[PUBMED]  [FULLTEXT]  
15.
Yunis JJ, Ramsay N. Retinoblastoma and subband deletion of chromosome 13. Am J Dis Child 1978;132:161-63.  Back to cited text no. 15
[PUBMED]  [FULLTEXT]  
16.
Turleau C, De Grouchy J. Constitutional karyotypes in retinoblastoma. Ophthalmic Paediatr Genet 1987;8:11-17.  Back to cited text no. 16
[PUBMED]  [FULLTEXT]  
17.
Gallie BL. Retinoblastoma: What is a gene like that doing in a place like this? Annals RCPSC 1992;25:2:117-20.  Back to cited text no. 17
    
18.
Lohmann DR, Brandt B, Hopping W, Passarge E, Horsthemke B. Spectrum of RB1 germ-line mutations in hereditary retinoblastoma. Am J Hum Genet 1996;58:940-49.  Back to cited text no. 18
[PUBMED]  [FULLTEXT]  
19.
Lohmann DR, Gerick M, Brandt B, Oelschalager U, Lorenz B, Passarge E, Horsthemke B. Constitutional RB1 gene mutations in patients with isolated unilateral retinoblastoma. Am J Hum Genet 1997;61:282-94.  Back to cited text no. 19
    
20.
Toguchida J, McGee TL, Paterson JC, Eagle JR, Tucker S, Yandell DW, et al. Complete genomic sequence of the human retinoblastoma susceptibility gene. Genomics 1993;17:535-43.  Back to cited text no. 20
[PUBMED]  [FULLTEXT]  
21.
Hamel PA, Gallie BL, Philips RA. The retinoblastoma protein and cell cycle regulation. Trends Med Genet 1992;8:5:180-85.  Back to cited text no. 21
    
22.
Hayashi N, Ido E, Obstuki Y and Ueno H. An Experimental Application of Gene Therapy for Human Retinoblastoma. IOVS 1999;40:265-72.  Back to cited text no. 22
    
23.
Emery AEH. Methodology in Medical Genetics. 2nd ed. Edinburugh: Churchill Livingstone;1986. PP37-54.  Back to cited text no. 23
    
24.
Rooney DE, Czepulkowski BH. Lymphocyte culture. In: Rickwood and Hames, editors. Human Cytogenetics Constitutional Analysis. A Practical Approach. IRL Press; Vol I, 1992. PP 31-54.  Back to cited text no. 24
    
25.
Pramanik R, Paral CC, Ghosh A. Pattern of solid malignant tumours in children - a ten year study. J Indian Med Assoc 1997;95:107-8,115.  Back to cited text no. 25
[PUBMED]  [FULLTEXT]  
26.
Verma IC, Sharma V, Sarkar TS. Genetic studies of retinoblastoma in India. In: Utsunomiya J, Mulvihill JJ, Weber W, editors. Familior Cancer and Prevention. New York; Wiley-Liss 1999. pp 485-92.  Back to cited text no. 26
    
27.
Nandakumar A. Anantha N, Appaji L, Swamy K, Mukherjee G, Venugopal T, et al. Descriptive epidemiology of childhood cancers in Bangalore, India. Cancer Causes Control 1996;7:405-10.  Back to cited text no. 27
    
28.
Sahu S, Banavali SD, Pai SK, Nair CN, Kurkure PA, Motwani SA, et al. Retinoblastoma: problems and perspectives from India. Pediatr Hematol Oncol 1998;15:501-08.  Back to cited text no. 28
[PUBMED]  [FULLTEXT]  
29.
Shields CL, Shields JA, Donoso LA. Clinical Genetics of Retinoblastoma. Int Ophthalmol Clin 1993;33:67-76.  Back to cited text no. 29
[PUBMED]  [FULLTEXT]  
30.
Mastrangelo D, Squitieri N, Bruni S, Hadjistilianou T, Frezzotti R. The Polymerase Chain Reaction (PCR) in the routine genetic characterization of retinoblastoma: a tool of the clinical laboratory. Surv Ophthalmol 1997;41:331-40.  Back to cited text no. 30
[PUBMED]  [FULLTEXT]  
31.
Barkeley JS, Kalita BC. Retinoblastoma in an adult. Lancet 1977;2:508-09.  Back to cited text no. 31
    
32.
Biswas J, Shanmugam MP, Parikh S, Patwardhan D, Badrinath SS. Retinoblastoma in adults - report of two cases with histopathologic correlation. Asia Pacific J Ophthalmol 1996;8:10-14.  Back to cited text no. 32
    
33.
Munier FL, Wang MX, Spence MA, Thonney F, Balmer A, Pescia G, Donoso LA, Murphree AL. Pseudo low penetrance in retinoblastoma. Arch Ophthalmol 1993;111:1507-11.  Back to cited text no. 33
[PUBMED]  [FULLTEXT]  
34.
Dryja TP, Rapaport J, McGee TL, Nork TM, Schwartz TL. Molecular etiology of low-penetrance retinoblastoma in two pedigrees. Am J Hum Genet 1993;52:1122-28.  Back to cited text no. 34
[PUBMED]  [FULLTEXT]  
35.
Bittles AH, Mason WM, Greene J, Rao NA. Reproductive behaviour and health in consanguineous marriages. Science 1991;252:789-94.  Back to cited text no. 35
[PUBMED]  [FULLTEXT]  
36.
Vogel F. Genetics of Retinoblastoma. Hum Genet 1979;52:1-54.  Back to cited text no. 36
[PUBMED]  [FULLTEXT]  
37.
Kloss K, Wahrisch P, Greger V, Messmer E, Fritze H, Hopping W, et al. Characterization of deletions at the retinoblastoma locus in patients with bilateral retinoblastoma. Am J Med Genet 1991;39:196-200.  Back to cited text no. 37
[PUBMED]  [FULLTEXT]  
38.
Bunin GR, Emanuel BS, Meadows AT, Buckley JD, Woods WG, Hammond GD. Frequency of 13q abnormalities among 203 patients with retinoblastoma. J Natl Cancer Inst 1989;81:370-74.  Back to cited text no. 38
[PUBMED]  [FULLTEXT]  
39.
Potluri VR, Helson L, Ellsworth RM, Reid T, Gilbert F. Chromosomal abnormalities in human retinoblastoma. Cancer 1986;58:663-71.  Back to cited text no. 39
[PUBMED]  [FULLTEXT]  
40.
Turleau C, Grouchy JD, Chavin-Colin F, Junien C, Seger J, Schlienger P, et al. Cytogenetic forms of retioblastoma: Their incidence in a survey of 66 patients. Cancer Genet Cytogenet 1985;16:321-32.  Back to cited text no. 40
    
41.
Ribeiro MCM, Andrade JAD, Erwenne CM, Brunoni D. Bilateral retinoblastoma associated with 13q - mosaicism. Possible manifestation of a germinal mutation. Cancer Genet Cytogenet 1987;2.  Back to cited text no. 41
    
42.
Motegi T. Lympocyte chromosome survey in 42 patients with retinoblastoma: Effort to detect 13q14 deletion mosaicism. Hum Genet 1981;58:168-73.  Back to cited text no. 42
[PUBMED]  [FULLTEXT]  
43.
Orye E, Benoit Y, Coppieters R, Jeannin P, Vercruysse C, Delaey J, et al. A case of retinoblastoma, assoicated with histiocytosis - X and mosaicism of a deleted D - group chromosome (13q14. q31). Clin Genet 1982;22:37-39.  Back to cited text no. 43
[PUBMED]  [FULLTEXT]  
44.
Davison EV, Gibbons B, Aherne GE, Roberts DF. Chromosomes in retinoblastoma patients. Clin Genet 1979;15:505-08.  Back to cited text no. 44
[PUBMED]  [FULLTEXT]  
45.
Motegi T. High rate of detection of 13q14 deletion mosaicism among retinoblastoma patients (using more extensive methods). Hum Genet 1982;61:95-97.  Back to cited text no. 45
[PUBMED]  [FULLTEXT]  
46.
Rosenberg C, Janson M, Nordeskjold M., Borresen AL. Morgante V. Intragenic organization of RB1 in a complex (4, 13) rearrangement demonstrated by FISH. Cytogenet Cell Genet 1994;65:268-71.  Back to cited text no. 46
    
47.
Selypes A, Laszlo A. Increased number of chromosome aberrations in the peripheral blood culture of a retinoblastoma petient. Acta Paediatrics Hungarica 1990;30:2:303-08.  Back to cited text no. 47
[PUBMED]  [FULLTEXT]  
48.
Mohney BG, Robertson DM, Schomberg PJ, Hodge DO. Second nonocular tumors in survivors of heritable retinoblastoma and prior radiation therapy. Am J Ophthalmol 1998;126:2:269-77.  Back to cited text no. 48
[PUBMED]  [FULLTEXT]  
49.
Hansen MF, Koufos A, Gallie BL, Phillips RA, Fodstad O, Brogger A, et al. Osteosarcoma and retinoblastoma: A shared chromosomal mechanism revealing recessive predisposition. Proc. Natl. Acad. Sci. USA 1985;82:6216-20.  Back to cited text no. 49
[PUBMED]  [FULLTEXT]  
50.
Yin Z, Spitz MR, Babaian RJ, Strom SS, Troncoso P, Kagan J. Limiting the location of a putative human prostate cancer tumor suppressor gene at chromosome 13q14.3. Oncogene 1999;18:52:7576-83.  Back to cited text no. 50
[PUBMED]  [FULLTEXT]  
51.
Eiriksdottir G, Johannesdottir G, Ingvarsson S, Bjornsdottir IB, Jonasson JG, Agnarsson BA, et al. Mapping loss of heterozygosity at chromosome 13q:loss at 13q12-q13 is associated with breast tumour progression and poor prognosis. Eur J Cancer 1998;34:13:2076-81.  Back to cited text no. 51
[PUBMED]  [FULLTEXT]  
52.
Simpson DJ, Magnay J, Bicknell JE, Barkan AL, McNicol AM, Clayton RN, et al. Chromosome 13q deletion mapping in pituitary tumors: In infrequent loss of the retinoblastoma susceptibility gene (RB1) locus depsite loss of RB1 protein product in somatotrophinomas. Cancer Res 1999;59:7:1562-66.  Back to cited text no. 52
[PUBMED]  [FULLTEXT]  
53.
Cairns P, Proctor AJ, Knowles MA. Loss of heterozygosity at the RB locus in frequent and correlates with muscle invasion in bladder carcinoma. Oncogene 1991;6:12:2305-09.  Back to cited text no. 53
[PUBMED]  [FULLTEXT]  
54.
Noorani HZ, Khan HN, Gallie BL, Detsky AS. Cost comparison of molecular versus conventional screening of relatives at risk for retinoblastoma. Am J Hum Genet 1996;59:301-07.  Back to cited text no. 54
[PUBMED]  [FULLTEXT]  
55.
Yandell DW, Campbell TA, Dayton SH, Petersen R, Walton D, Little JB, et al. Oncogenic point mutations in the human retinoblastoma gene: their application to genetic counseling. N Engl J Med 1989;321:1689-95.  Back to cited text no. 55
    
56.
Onadim Z, Hykin PG, Hungerford JL, Cowell JK. Genetic counselling in retinoblastoma: importance of ocular fundus examination of first degree relatives and linkage analysis. Br J Ophthalmol 1991;75:147-50.  Back to cited text no. 56
[PUBMED]  [FULLTEXT]  
57.
Smith BJ, O'Brien JM. The genetics of retinoblastoma and current diagnostic testing. J Pediatr Ophthalmol Strabismus 1996;33:120-23.  Back to cited text no. 57
[PUBMED]  [FULLTEXT]  
58.
Mukai S. Molecular genetic diagnosis of retinoblastoma. Semin Ophthalmol 1993;8:4:292-99.  Back to cited text no. 58
    
59.
Harbour JW. Overview of RB gene mutations in patients with retinoblastoma. Implications for clinical genetic screening. Ophthalmology 1998;105:1442-47.  Back to cited text no. 59
[PUBMED]  [FULLTEXT]  
60.
Musarella MA, Gallie BL. A simplified scheme for genetic counseling in retinoblastoma. J Pediatr Ophthalmol Strabismus 1987;24:124-25.  Back to cited text no. 60
[PUBMED]  [FULLTEXT]  
61.
Sippel KC, Fraioli RE, Smith GD, Schalkoff ME, Sutherland J, Gallie BL, et al. Frequency of somatic and germ-line mosaicism in retinoblastoma: Implications for genetic counseling. Am J Hum Genet 1998;62:610-19.  Back to cited text no. 61
[PUBMED]  [FULLTEXT]  


    Figures

  [Figure - 1], [Figure - 2], [Figure - 3], [Figure - 4]


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