Xp22.2-3 Loss of Heterozygosity Is Associated with Germline BRCA1 Mutation in Ovarian Cancer

Buekers, Thomas E.; Lallas, Thomas A.; Buller, Richard E.

doi:10.1006/gyno.1999.5713

Cited by 18 publications

(20 citation statements)

References 14 publications

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“…Five tumors showed loss of most (#11, 15,22) or all (#10, 23) informative markers. Four atypical carcinoids showed partial (#13b, 24) or interstitial (#17, 25) losses.…”

Section: Resultsmentioning

confidence: 99%

“…22 Moreover, LOH at pseudoautosomal regions at the end of Xp (Xp22.3) and Xq (Xq28) arms was found in sporadic breast cancers, in association with negative hormonal receptor phenotype, an indicator of poorer prognosis and more aggressive behavior in these neoplasms. 23 Microsatellite MAOA at Xp11.4-Xp11.3 is a dinucleotide repeat included in the monoamine oxidase A gene, which encodes for a mitochondrial outer membrane protein implicated in the catabolism of neuroactive and vasoactive amines in the central nervous system and in peripheral tissues.…”

Section: Discussionmentioning

confidence: 99%

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Malignancy-associated X chromosome allelic losses in foregut endocrine neoplasms: further evidence from lung tumors

et al. 2005

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Association of X chromosome allelic losses with tumor malignancy has been identified in foregut but not in midgut endocrine neoplasms. The aim of this study was to investigate the association of deletions on X chromosome with malignancy in lung neuroendocrine tumors, another family of foregut neoplasms comprising four categories with increased malignancy: typical and atypical carcinoids, large cell neuroendocrine and small cell lung carcinomas. To evaluate loss of heterozygosity, DNA extracted from nine typical carcinoids, 17 atypical carcinoids, six large cell neuroendocrine carcinomas and five small cell lung carcinomas was PCRamplified for 18 microsatellite markers spanning the whole X chromosome. All tissue samples were formalinfixed and paraffin-embedded. X chromosome losses were absent in typical carcinoids, whereas they were found in nine out of 17 atypical carcinoids and in five out of six large cell neuroendocrine carcinomas (involving 28 and 70% of informative loci, respectively). On the contrary, deletions on X chromosome were an extremely rare event in small cell lung carcinomas. In atypical carcinoids, the presence of losses was associated with larger tumor size, higher pT status and advanced stage. No death occurred in atypical carcinoid patients without deletions on X chromosome, whereas all atypical carcinoid patients who had died from disease showed allelic losses. In conclusion, X chromosome allelic losses, absent in benign 'typical' carcinoids, progressively increased in frequency from intermediate-grade 'atypical' carcinoids to high-grade large cell neuroendocrine carcinomas. These results extend the association of deletions on X chromosome with malignancy, already demonstrated in other foregut endocrine neoplasms, to lung neuroendocrine tumors. The absence of X chromosome allelic losses in small cell lung carcinomas underlines a striking difference from large cell neuroendocrine carcinomas, possibly linked to different pathogenetic mechanisms of these two highly aggressive neuroendocrine lung tumors.

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“…Five tumors showed loss of most (#11, 15,22) or all (#10, 23) informative markers. Four atypical carcinoids showed partial (#13b, 24) or interstitial (#17, 25) losses.…”

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Malignancy-associated X chromosome allelic losses in foregut endocrine neoplasms: further evidence from lung tumors

et al. 2005

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“…More recent studies showed that activation or inactivation of certain X-linked genes is a predisposing factor for breast cancer (11). Furthermore, skewed Xi was shown to be a predisposing factor for the development of invasive ovarian cancer and early onset of breast cancer (12,13). The role of X-chromosome dosage in cancer is further supported with the observation that 47 XXY males have increased predisposition for breast cancer compared with 46 XY males (14,15).…”

Section: Introductionmentioning

confidence: 88%

Aberrant Expression of X-Linked Genes RbAp46, Rsk4, and Cldn2 in Breast Cancer

Thakur

Rahman

et al. 2007

Molecular Cancer Research

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The consequence of activation status or gain/loss of an X-chromosome in terms of the expression of tumor suppressor genes or oncogenes in breast cancer has not been clearly addressed. In this study, we investigated the activation status of the X-chromosomes in a panel of human breast cancer cell lines, human breast carcinoma, and adjacent mammary tissues and a panel of murine mammary epithelial sublines ranging from low to high invasive potentials. Results show that most human breast cancer cell lines were homozygous, but both benign cell lines were heterozygous for highly polymorphic X-loci (IDS and G6PD). On the other hand, 60% of human breast carcinoma cases were heterozygous for either IDS or G6PD markers. Investigation of the activation status of heterozygous cell lines revealed the presence of only one active X-chromosome, whereas most heterozygous human breast carcinoma cases had two active X-chromosomes. Furthermore, we determined whether or not an additional active X-chromosome affects expression levels of tumor suppressor genes and oncogenes. Reverse transcription-PCR data show high expression of putative tumor suppressor genes Rsk4 and RbAp46 in 47% and 79% of breast carcinoma cases, respectively, whereas Cldn2 was down-regulated in 52% of breast cancer cases compared with normal adjacent tissues. Consistent with mRNA expression, immunostaining for these proteins also showed a similar pattern. In conclusion, our data suggest that high expression of RbAp46 is likely to have a role in the development or progression of human breast cancer. The activation status of the X-chromosome may influence the expression levels of X-linked oncogenes or tumor suppressor genes. (Mol Cancer Res 2007;5(2):171 -81)

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“…Loss of (part of) the X chromosome has been detected in unselected ovarian cancer cases (Table 2) and was also frequent in our tumor panel (14 of 36; 39%). Interestingly, inactivation of the X chromosome, specifically Xp22.2-3 of the active allele, has recently been suggested to encode a product that specifically interacts with BRCA1 in some hereditary ovarian cancers (Buekers et al, 2000). Chromosome 18q21 harbors three candidate tumor suppressor genes; the SMAD4 gene located on this band was recently found to be mutated in ovarian cancer (Takakura et al, 1999).…”

Section: Lossesmentioning

confidence: 99%

Comparative Genomic Hybridization of Microdissected Familial Ovarian Carcinoma: Two Deleted Regions on Chromosome 15q Not Previously Identified in Sporadic Ovarian Carcinoma

Zweemer

Ryan

Snijders

et al. 2001

Laboratory Investigation

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SUMMARY:The vast majority of familial ovarian cancers harbor a germline mutation in either the breast cancer gene BRCA1 or BRCA2 tumor suppressor genes. However, mutations of these genes in sporadic ovarian cancer are rare. This suggests that in contrast to hereditary disease, BRCA1 and BRCA2 are not commonly involved in sporadic ovarian cancer and may indicate that there are two distinct pathways for the development of ovarian cancer. To characterize further differences between hereditary and sporadic cancers, the comparative Comparison with the literature revealed that the majority of these genetic alterations are also common in sporadic ovarian cancer. Deletions of 15q11-15, 15q24 -25, 8p21-ter, 22q13, 12q24 and gains at 11q22, 13q22, and 17q23-25, however, appear to be specific to hereditary ovarian cancer. Aberrations at 15q11-15 and 15q24 -25 have not yet been described in familial ovarian cancer. In these regions, important tumor suppressor genes, including the hRAD51 gene, are located. These and other yet unknown suppressor genes may be involved in a specific carcinogenic pathway for familial ovarian cancer and may explain the distinct clinical presentation and behavior of familial ovarian cancer. (Lab Invest 2001, 81:1363-1370.

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Xp22.2-3 Loss of Heterozygosity Is Associated with Germline BRCA1 Mutation in Ovarian Cancer

Cited by 18 publications

References 14 publications

Malignancy-associated X chromosome allelic losses in foregut endocrine neoplasms: further evidence from lung tumors

Malignancy-associated X chromosome allelic losses in foregut endocrine neoplasms: further evidence from lung tumors

Aberrant Expression of X-Linked Genes RbAp46, Rsk4, and Cldn2 in Breast Cancer

Comparative Genomic Hybridization of Microdissected Familial Ovarian Carcinoma: Two Deleted Regions on Chromosome 15q Not Previously Identified in Sporadic Ovarian Carcinoma

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