Original article
Loss of 10p material in a child with human papillomavirus–positive disseminated bilateral retinoblastoma

https://doi.org/10.1016/j.cancergencyto.2005.01.012Get rights and content

Abstract

Retinoblastoma (RB) is a malignant childhood tumor that results from loss or inactivation of both alleles of the RB1 gene. Human papillomavirus (HPV) DNA sequences have been found in RB tissue, suggesting a role of the viral infection with RB. We here describe a child with disseminated bilateral RB without familial history, who displayed a loss of material from 10p. Fluorescence in situ hybridization studies showed a somatic loss of both alleles of the RB1 gene. Moreover, sequences for HPV-6a were detected on DNA extracted from eye tumor tissue and from nonstimulated peripheral blood leukocyte cultures. The eye tumor tissue was also positive for HPV L1 viral proteins. Repeated loss of the short arm of chromosome 10 in HPV-transfected keratinocytes has been reported. Loss of heterozygosity in 10p14∼p15 is also frequent in cervical cancers. Therefore, it seems probable that the abnormalities on 10p detected in the present case are related to the HPV infection. Thus, HPV could be a cofactor in the progression of RB by promoting nonrandom additional mutations.

Introduction

Retinoblastoma (RB) is a malignant childhood tumor that occurs as familial or sporadic forms and may be unilateral or bilateral [1]. Partial loss of the chromosomal band 13q14 is a frequent primary change observed in RB with a consequent loss of one or both alleles of the RB1 gene [1], [2], [3], [4], [5], [6], [7], [8]. A great heterogeneity in secondary chromosomal abnormalities associated with clonal evolution of RB also has been described: the most important are −13, −16/loss 16q, and −17/loss 17p [7], [8]. Human papillomavirus (HPV) DNA sequences have been found recently in RB tissue, suggesting that this viral infection plays a role in the genesis or progression of RB [9], [10]. In this report we describe a child with disseminated bilateral RB who displayed a deletion of 10p11 and an idic(10)(p11). A deletion of the RB1 gene was also detected. Moreover, he was positive for HPV DNA sequences and L1 viral proteins.

Section snippets

Case report

A 9-month-old child was diagnosed as having sporadic bilateral RB. The right eye was enucleated, and cryotherapy to the left eye was applied. Histopathologic analysis of the enucleated eye displayed a choroid massive invasion. Chemotherapy consisting of carboplatin and etoposide was administered every month for the following 11 months, and he went into remission. At the 14th month after diagnosis, the patient worsened. Physical examination revealed fever, blepharitis, bilateral axilla adenitis,

Cytogenetic studies

Three cytogenetic studies were performed. The first one was done at diagnosis and consisted of peripheral blood lymphocytes stimulated with phytohemagglutinin and harvested by standard methods. The second and third studies were performed from peripheral blood cells without stimulation, taken 14 and 16 months after diagnosis, respectively. These cells were cultured for 2 and 24 hours and harvested. The chromosomal preparations were GTG and CBG banded. Karyotypes were described according to the

Cytogenetic studies

The karyotype from phytohemagglutinin-stimulated peripheral blood cells was 46,XY[16]. The cytogenetic study conducted at the 14th month after diagnosis displayed the karyotype 46,XY,idic(10)(p11)[10]/46,XY,del(10)(p11)[2]/46,XY[7] (Fig. 1, A–D). In the third study (at the 16th month) the following karyotype was found: 46,XY,del(10)(p11)[15]/46,XY,idic(10)(p11)[10].

FISH studies

FISH with the RB1 probe showed signals on both chromosomes 13 in phytohemagglutinin-stimulated patient cells (Fig. 1E). In

Discussion

There are 101 cases of RB recorded in the Mitelman database of chromosomal aberrations in cancer (MDCAC) [7], yet neither del(10)(p11) nor idic(10)(p11) have been detected in RB, so the present findings are novel and perhaps related to the clonal evolution of RB. Furthermore, both chromosomal abnormalities have been detected in other malignancies [7], [8], [12], [13], [14], [15]. There are 228 cases of del(10)(p) recorded in the MDCAC found in diverse tumors, but it was the sole abnormality in

Acknowledgments

We thank Dr. Horacio Rivera for his critical review of the manuscript. Juan Pablo Meza Espinoza and Verónica Judith Picos Cárdenas have been supported by CONACyT fellowships.

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