Emerging role of long non-coding RNA JPX in malignant processes and potential applications in cancers / 中华医学杂志(英文版)

Long non-coding RNAs (lncRNAs) reportedly function as important modulators of gene regulation and malignant processes in the development of human cancers. The lncRNA JPX is a novel molecular switch for X chromosome inactivation and differentially expressed JPX has exhibited certain clinical correlations in several cancers. Notably, JPX participates in cancer growth, metastasis, and chemoresistance, by acting as a competing endogenous RNA for microRNA, interacting with proteins, and regulating some specific signaling pathways. Moreover, JPX may serve as a potential biomarker and therapeutic target for the diagnosis, prognosis, and treatment of cancer. The present article summarizes our current understanding of the structure, expression, and function of JPX in malignant cancer processes and discusses its molecular mechanisms and potential applications in cancer biology and medicine.

Pathogenetic mechanism for a female patient with hemophilia A / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To explore the pathogenetic mechanism for a female patient affected with hemophilia A (HA).</p><p><b>METHODS</b>Potential genetic defect was detected with inverse shifting-polymerase chain reaction (IS-PCR). The pattern of X chromosome inactivation was determined with a human androgen receptor assay (HUMARA assay). G-banded karyotyping was carried out to exclude potential chromosome aberrations.</p><p><b>RESULTS</b>IS-PCR showed that the defect of FVIII gene was the distal type of intron 22 inversion. The HUMARA assay showed that the X chromosome inactivation was non-random, and that the mother's X chromosome activity was lower than that of the father's X chromosome which has carried the inverted FVIII gene. No abnormalities were found with G-banded chromosomes.</p><p><b>CONCLUSION</b>The prevalence of female HA patient may be caused by non-random inactivation of X chromosomes.</p>

Analysis of C43G mutation in the promoter region of the XIST gene in patients with idiopathic primary ovarian insufficiency / 대한생식의학회지

OBJECTIVE: The XIST gene is considered to be an attractive candidate gene for skewed X-chromosome inactivation and a possible cause of primary ovarian insufficiency (POI). The purpose of this study was to investigate whether the XIST gene promoter mutation is associated with idiopathic POI in a sample of the Korean population. METHODS: Subjects consisted of 102 idiopathic POI patients and 113 healthy controls with normal menstrual cycles. Patients with the following known causes of POI were excluded in advance: cytogenetic abnormalities, prior chemo- or radiotherapy, or prior bilateral oophorectomy. Genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism analysis. RESULTS: The mean age of onset of ovarian insufficiency was 28.7+/-8.5 years and the mean values of serum luteinizing and follicle-stimulating hormones and estradiol in the POI group were 31.4+/-18.2 mIU/mL, 74.5+/-41.1 mIU/mL, and 30.5+/-36.7 pg/mL, respectively. We found no cytosine to guanine (C43G) variation in the XIST gene in both POI patients and controls. CONCLUSION: The C43G mutation in the promoter region of the XIST gene was not present in the Korean patients with idiopathic POI in our study, in contrast to our expectation, suggesting that the role of XIST in the pathogenesis of POI is not yet clear.

Hemophilia B in a female adolescent: A case report / Philippine Journal of Obstetrics and Gynecology

Hemophilia is a relatively rare bleeding disorder. It is an X-linked hereditary bleeding disorder caused by a deficient or defective coagulation factor VIII (Hemophilia A) or factor IX (Hemophilia B). Hemophilia A is more common than Hemophilia B. The X-linked inheritance pattern results in men expressing the disease and women typically being carriers. Under rare circumstances a woman can also show a bleeding phenotype.A 13 year-old female presented with profuse vaginal bleeding. She had history of several hospital admissions because of bleeding manifestations like hematuria and epistaxis. Based on the pedigree analysis and results of factor IX assay tests she was diagnosed to have Hemophilia B of moderate severity. She was given hormonal and non-hormonal treatments as well as blood transfusions which stop the bleeding and corrected the anemia. A multidisciplinary approach of management involving the gynecologist, hematologist and a geneticist will be beneficial to the patient.The inheritance, clinical manifestations, diagnosis and treatment of Hemophilia B in a female adolescent are discussed

Diagnosis of MECP2 duplication syndrome with molecular genetic techniques / 中华儿科杂志

<p><b>OBJECTIVE</b>To investigate whether the four boys with delayed motor development and intellectual disability suffer from MECP 2 duplication syndrome.</p><p><b>METHOD</b>Blood specimens and clinical data of four patients and mothers of patient 2 and patient 4 were collected. Genomic DNA was extracted from peripheral blood using DNA extraction kit. At first multiplex ligation-dependent probe amplification (MLPA) was employed in 4 patients, two distinct kits SALSA P036 and P070 for sub-telomere screening, and SALSA P245 for the 22 common microdeletion and microduplication syndromes. Then array-CGH analysis was carried out. Two mothers of patients were tested by array- comparative genomic hybridization (CGH) and X chromosome inactivation analysis.</p><p><b>RESULT</b>All the 4 patients presented with severe hypotonia, delayed motor development, intellectual disability and absent or limited language. Three patients manifested recurrent pneumonia in infancy except patient 2. Four patients had duplication on chromosome Xq28 with MLPA kit SALSA P245. Array-CGH identified the size of each duplication on Xq28. The precise size of each duplication was different in the four patients: patient 1, 14.931 Mb, patient 2, 0.393 Mb, patient 3, 0.482 Mb and patient 4, 0.299 Mb. To compare Xq28 duplications with UCSC database (http://genome.ucsc.edu/) revealed that each duplication harbors the MECP 2 and HCFC 1 gene. Mothers of patient 2 and patient 4 also carried microduplication on Xq28. X chromosome inactivation analysis demonstrated completely skewed inactivation (0: 100) and it is the inactive allele that passed on to the patients.</p><p><b>CONCLUSION</b>For patients that present with delayed motor development, intellectual disability, hypotonia, absent or limited language and recurrent infection, combination of MLPA and array- CGH is effective and specific diagnostic methods of MECP 2 duplication syndrome.</p>

Characterization of a prenatally diagnosed de novo der(X)t(X;Y)(q27;q11.23) of fetus

A 31-year-old woman, who was pregnant with twins, underwent chorionic villus sampling because of increased nuchal translucency in one of the fetuses. Cytogenetic analysis showed a normal karyotype in the fetus with increased nuchal translucency. However, the other fetus, with normal nuchal translucency, had a derivative X chromosome (der(X)). For further analysis, fluorescence in situ hybridization (FISH) and additional molecular studies including fragile X analysis were performed. FISH analysis confirmed that the Y chromosome was the origin of extra segment of the der(X). The X-chromosome breakpoint was determined to be at Xq27 by FMR1 CGG repeat analysis, and the Y-chromosome breakpoint was determined to be at Yq11.23 by the Y chromosome microdeletion study. To predict the fetal outcome, the X-inactivation pattern was examined, and it revealed non-random X inactivation of the der(X). To the best of our knowledge, the identification of an unbalanced Xq;Yq translocation at prenatal diagnosis has never been reported. This study was performed to identify precise breakpoints and the X-inactivation pattern as well as to provide the parents with appropriate genetic counseling.

MICrocephaly, disproportionate pontine and cerebellar hypoplasia syndrome: A clinico-radiologic phenotype linked to calcium/calmodulin-dependent serine protein kinase gene mutation.

MICrocephaly, disproportionate pontine and cerebellar hypoplasia (MICPCH) syndrome, a rare X-linked disorder, generally seen in girls, is characterized by neurodevelopmental delay, microcephaly, and disproportionate pontine and cerebellar hypoplasia. It is caused by inactivating calcium/calmodulin-dependent serine protein kinase (CASK) gene mutations. We report a 2-year-old girl with severe neurodevelopmental delay, microcephaly, minimal pontine hypoplasia, cerebellar hypoplasia, and normal looking corpus callosum, with whom the conventional cytogenetic studies turned out to be normal, and an array-comparative genomic hybridization (a-CGH) analysis showed CASK gene duplication at Xp11.4. Our case highlights the importance of using clinico-radiologic phenotype to guide genetic investigation and it also confirms the role of a-CGH analysis in establishing the genetic diagnosis of MICPCH syndrome, when conventional cytogenetic studies are inconclusive.

Determination of hematopoietic clonality by detection of multiple X-linked gene exonic polymorphic loci using transcription-based clonality assays / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the frequencies of heterozygosity in X-linked G6PD, P55, BTK, and FHL-1 gene exonic polymorphic loci among Chinese females and the value of determination of hematopoietic clonality by detection of these X-chromosome exonic polymorphisms based on X-chromosome inactivation patterns (XCIP)-transcription-based clonality assays (TCA).</p><p><b>METHODS</b>Genomic DNA was extracted from peripheral blood of 446 Chinese healthy females. Allele-specific PCR (ASPCR) or PCR-restriction enzyme digestion method was applied for detecting G6PD, P55, BTK and FHL-1 polymorphisms. Those heterozygotic loci were used as markers to examine the hematopoietic clonality of bone marrow mononuclear cells by TCA from essential thrombocythemia (ET) patients with JAK2V617F mutation and myelodysplastic syndrome (MDS) patients with abnormal karyotype.</p><p><b>RESULTS</b>Among the total 446 genomic DNA samples, the frequencies of heterozygosity in G6PD, P55, BTK and FHL-1 loci were 12.8%, 29.4%, 52.0% and 46.4%, respectively. About 81.4% of females were heterozygous at one or more loci. All 10 ET patients with JAK2V617F mutation and 2 MDS patients with abnormal karyotype, which were heterozygotic in either locus, had monoclonal/oligoclonal hematopoiesis.</p><p><b>CONCLUSION</b>Clonality detection based on X chromosome inactivation patterns-transcription based clonality assays is applicable to about 80% of Chinese females.</p>

Analysis of the parental origin of de novo MECP2 mutations and X chromosome inactivation in fifteen sporadic cases with Rett syndrome / 中华儿科杂志

<p><b>OBJECTIVE</b>Rett syndrome (RTT) is a neurodevelopmental disorder occurring almost exclusively in females as sporadic cases due to de novo mutations in the methyl-CpG-binding protein 2 gene (MECP2). Familial cases of RTT are rare and are due to X-chromosomal inheritance from a carrier mother. Recently, DNA mutations in the MECP2 have been detected in approximately 84.7% of patients with RTT in China. To explain the sex-limited expression of RTT, it has been suggested that de novo X-linked mutations occur exclusively in male germ cells resulting therefore only in affected daughters. To test this hypothesis, we have analyzed the parental origin of mutations and the XCI status in 15 sporadic cases with RTT due to MECP2 molecular defects.</p><p><b>METHODS</b>Allele-specific PCR was performed to amplify a fragment including the position of the mutation. The allele-specific PCR products were sequenced to determine which haplotype contained the mutation. It was then possible to determine the parent of origin by genotyping the single nucleotide polymorphism (SNP) in the parents. The degree of XCI and its direction relative to the X chromosome parent of origin were measured in DNA prepared from peripheral blood leucocytes by analyzing CAG repeat polymorphism in the androgen receptor gene (AR).</p><p><b>RESULTS</b>Except for 2 cases who had a frameshift mutation; all the remaining 13 cases had a C-->T transition mutation. Paternal origin has been determined in all cases with the C-->T transition mutation. For the two frameshift mutations, paternal origin has been determined in one case and maternal origin in the other. The frequency of male germ-line transmission in mutations is 93.3%. Except for 2 cases who were homozygotic at the AR locus, of the remaining 13 cases, 8 cases had a random XCI pattern; the other five cases had a skewed XCI pattern and they favor expression of the maternal origin allele.</p><p><b>CONCLUSION</b>De novo mutations in sporadic RTT occur almost exclusively on the paternally derived X chromosome and that this is most probably the cause for the high female: male ratio observed in sporadic cases with RTT. Random XCI was the main XCI pattern in sporadic RTT patients. The priority inactive X chromosome was mainly of paternal origin.</p>

Cryptic mosaicism involving a second chromosome X in patients with Turner syndrome

The high abortion rate of 45,X embryos indicates that patients with Turner syndrome and 45,X karyotype could be mosaics, in at least one phase of embryo development or cellular lineage, due to the need for the other sex chromosome presence for conceptus to be compatible with life. In cases of structural chromosomal aberrations or hidden mosaicism, conventional cytogenetic techniques can be ineffective and molecular investigation is indicated. Two hundred and fifty patients with Turner syndrome stigmata were studied and 36 who had female genitalia and had been cytogenetically diagnosed as having "pure" 45,X karyotype were selected after 100 metaphases were analyzed in order to exclude mosaicism and the presence of genomic Y-specific sequences (SRY, TSPY, and DAZ) was excluded by PCR. Genomic DNA was extracted from peripheral blood and screened by the human androgen receptor (HUMARA) assay. The HUMARA gene has a polymorphic CAG repeat and, in the presence of a second chromosome with a different HUMARA allele, a second band will be amplified by PCR. Additionally, the CAG repeats contain two methylation-sensitive HpaII enzyme restriction sites, which can be used to verify skewed inactivation. Twenty-five percent (9/36) of the cases showed a cryptic mosaicism involving a second X and approximately 14 percent (5/36), or 55 percent (5/9) of the patients with cryptic mosaicism, also presented skewed inactivation. The laboratory identification of the second X chromosome and its inactivation pattern are important for the clinical management (hormone replacement therapy, and inclusion in an oocyte donation program) and prognostic counseling of patients with Turner syndrome.

Evaluación del patrón de inactivación del cromosoma X en portadoras sintomáticas y mujeres con hemofilia / Assessing the inactivation pattern in chromosome X among symptomatic carriers and women with haemophilia

La inactivación del cromosoma X es un fenómeno estocástico que ocurre en la embriogénesis temprana femenina para lograr una compensación de dosis génica respecto a los varones. Ciertos mecanismos genéticos afectan el proceso normal, propiciando una inactivación sesgada con efectos clínicos relevantes en portadoras de trastornos recesivos ligados al cromosoma X, como la hemofilia. La herramienta molecular mayormente utilizada para la evaluación del patrón de inactivación del cromosoma X es la amplificación por PCR del gen del receptor de andrógenos humano (HUMARA). El empleo de esta técnica en portadoras sintomáticas y mujeres con hemofilia permite esclarecer si las manifestaciones de la enfermedad se deben a una lyonización desfavorable. Estos estudios, además, son importantes para la comprensión del proceso de inactivación del cromosoma X en humanos.

X chromosome inactivation is a stochastic event that occurs early in female embryo development to achieve dosage compensation with males. Certain genetic mechanisms affect the normal process causing a skewed X inactivation pattern which has clinical relevance in female carriers of X-linked recessive disorders, like haemophilia. The most commonly used assay to evaluate the X inactivation pattern is the PCR amplification of the human androgen receptor gene (HUMARA). The use of this technique in bleeding carriers and women with haemophilia allows identifying if their hemorrhagic symptoms are due to an unfavourable lyonization. Furthermore, these studies are important for understanding the X chromosome inactivation process in humans.

Understanding of epigenetics and DNA methylation

Unbalanced X; autosome translocation.

Unbalanced X; autosome translocation can result in multiple congenital abnormalities/mental retardation syndrome due to chromosomal imbalance. Here is described a patient with developmental delay, microcephaly, agenesis of corpus callosum, spasticity, seizures and dysmorphism as a result of meiotic malsegregation of balanced X; autosome translocation in mother. Present case signifies the importance of chromosomal analysis in a patient with developmental delay/ mental retardation and discuss lyonization in cases with X; autosome translocation.

X-chromosomal inactivation skewing in blood cells is associated with early development of lung / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To observe the relationship between skewed X-chromosomal inactivation (SXCI) and development of lung cancer in females.</p><p><b>METHODS</b>DNA was isolated from peripheral blood cells from patients with primary lung cancer (n = 148) and control subjects (n =289). Exon 1 of androgen receptor ( AR) gene was amplified, with its products from different alleles resolved on denaturing polyacrylamide gels and visualized by silver staining. The corrected ratio (CR) between products from different AR alleles before and after Hpa II pretreatment was calculated. All statistical tests were two-sided.</p><p><b>RESULTS</b>With CR> or = 10 adopted as the criterion, SXCI was found more frequently in the younger patients ( C50 years; 7. 9%) than in the controls of the same age group (1. 2% ; P = 0. 046). The SXCI frequency, however, were not significantly different between the old patients ( > 50 years; 4. 5% ) and the controls of the same age group (5. 4% ; P =0. 488). Whether taking CR> or =3 or CR> or =10 as the criteria, the average ages of the patients with SXCI were more than 10 years younger than those without SXCI (P < 0. 05).</p><p><b>CONCLUSION</b>SXCI in blood cells is associated with early development of lung cancer in females.</p>

X chromosome inactivation patterns in patients with Rett syndrome and their mothers and the parental origin of the priority inactive X chromosome / 中华儿科杂志

<p><b>OBJECTIVE</b>Rett syndrome (RTT) is a severe childhood neurodevelopmental disorder mainly affecting females. The pathogenic gene is located at Xq28, which codes for the methyl-CpG-binding protein 2. MECP2 gene is affected by X chromosome inactivation (XCI). The different XCI patterns of females could affect the expression ratios of pathogenic gene, causing changes in clinical symptoms. In order to understand the XCI patterns in RTT patients and the relationship between XCI pattern, genotype and phenotype, the XCI patterns in patients with RTT and their mothers, the parental origin of the priority inactive X chromosome in RTT, and the relations of XCI patterns with genotype and phenotype in RTT cases were analyzed.</p><p><b>METHODS</b>Genomic DNA was extracted from peripheral blood of 55 cases with RTT (52 with MECP2 mutations, 3 without mutations), 53 mothers of RTT cases and 48 normal female controls. DNA was digested with methylation sensitive restriction endonuclease Hpa II. Then the undigested and digested DNAs were amplified via PCR for the first exon of human androgen receptor (AR) gene. PCR products were analyzed by Genescan.</p><p><b>RESULTS</b>The heterozygotic rates of AR gene were 82%, 77% and 83% in RTT patients, mothers and controls, respectively. XCI distribution pattern of RTT was different from that of the mothers and control, P < 0.05. More mothers and controls than RTT patients were in the area of XCI 50:50 - 59:41. The differences between them were statistically significant (P < 0.05). No significant difference in XCI distribution patterns between mothers and the control groups was found (P > 0.05). Non-random XCI rates in the areas of XCI >or= 65:35 and >or= 80:20 were 53.35% and 17.8%, respectively, in RTT patients, compared with the mothers group (36.6%, 7.3%) and control group (35%, 10%), it was higher in RTT patients, but the difference was not statistically significant (P > 0.05). In 18 of 21 cases with XCI >or= 65:35, the priority inactive X chromosome was of paternal origin (85.7%). Variable XCI patterns were observed in the same gene mutation patients. The highly skewed XCI as well as the random XCI were found in patients with mild, severe and typical phenotype. The rate of highly skewed XCI in atypical patients was higher than that in typical RTT patients. The rate of highly skewed XCI in T158M was higher than the other type mutations. No highly skewed XCI was observed in cases with R133C mutation.</p><p><b>CONCLUSION</b>The XCI distribution pattern of RTT patients was different from that of RTT mother and control groups. There was no significant difference in XCI distribution patterns between mothers and the control groups. It was not a main genetic pattern in RTT that mothers as the carriers to transmit the pathogenic gene to the patients. Non-random XCI was not the main XCI pattern in RTT patients. The priority inactive X chromosome was mainly of paternal origin. XCI could modify the clinical phenotype of RTT, but had limitations in explaining all the phenotypes manifested in RTT cases.</p>

Clonality study of palmar fibromatosis / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clonality of palmar fibromatosis by molecular genetic analysis of X chromosome inactivation pattern at a polymorphic site of human androgen receptor gene (HUMARA).</p><p><b>METHODS</b>Twelve female cases of palmar fibromatosis were enrolled into this study. Hematoxylin and eosin-stained sections of paraffin-embedded, formalin-fixed tissues were microdissected by laser capture microdissection technology in order to obtain the proliferative spindle cells. Tumor cells isolated from rectal adenocarcinoma in a female patient were used as positive control. The genomic DNAs were extracted with phenol and chloroform, digested with methylation-sensitive restriction endonuclease HpaII, and amplified by polymerase chain reaction (PCR) using primers targeted to a highly polymorphic short tandem repeat of HUMARA. The amplimers were separated on vertical 8% non-denaturing polyacrylamide gels and the patterns were visualized with ethidium bromide stain.</p><p><b>RESULTS</b>The methodology for clonality analysis was validated in the positive control using rectal adenocarcinoma cells. Among the 12 cases studied, PCR amplification failed in 3 samples and 1 sample showed homozygosity which was not suitable for further analysis. Eight samples were successfully amplified and showed a random X chromosome inactivation pattern, suggesting polyclonality in these lesions.</p><p><b>CONCLUSIONS</b>Palmar fibromatosis is a polyclonal condition and should be considered as a form of non-neoplasmic fibroblastic proliferation.</p>

Study of androgen receptor and phosphoglycerate kinase gene polymorphism in major cellular components of the so-called pulmonary sclerosing hemangioma / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clonality of polygonal cells and surface cuboidal cells in the so-called pulmonary sclerosing hemangioma (PSH).</p><p><b>METHODS</b>17 female surgically resected PSH were found. The polygonal cells and surface cuboidal cells of the 17 PSH cases were microdissected from routine hematoxylin and eosin-stained sections. Genomic DNA was extracted, pretreated through incubation with methylation-sensitive restrictive endonuclease HhaI or HpaII, and amplified by nested polymerase chain reaction for X chromosome-linked androgen receptor (AR) and phosphoglycerate kinase (PGK) genes. The length polymorphism of AR gene was demonstrated by denaturing polyacrylamide gel electrophoresis and silver staining. The PGK gene products were treated with Bst XI and resolved on agarose gel.</p><p><b>RESULTS</b>Amongst the 17 female cases of PSH, 15 samples were successfully amplified for AR and PGK genes. The rates of polymorphism were 53% (8/15) and 27% (4/15) for AR and PGK genes respectively. Polygonal cells and surface cuboidal cells of 10 cases which were suitable for clonality study, showed the same loss of alleles (clonality ratio = 0) or unbalanced methylation pattern (clonality ratio < 0.25).</p><p><b>CONCLUSIONS</b>The polygonal cells and surface cuboidal cells in PSH demonstrate patterns of monoclonal proliferation, indicating that both represent true neoplastic cells.</p>

Ectopic development of skeletal muscle induced by subcutaneous transplant of rat satellite cells

The present study analyzes the ectopic development of the rat skeletal muscle originated from transplanted satellite cells. Satellite cells (10(6) cells) obtained from hindlimb muscles of newborn female 2BAW Wistar rats were injected subcutaneously into the dorsal area of adult male rats. After 3, 7, and 14 days, the transplanted tissues (N = 4-5) were processed for histochemical analysis of peripheral nerves, inactive X-chromosome and acetylcholinesterase. Nicotinic acetylcholine receptors (nAChRs) were also labeled with tetramethylrhodamine-labeled alpha-bungarotoxin. The development of ectopic muscles was successful in 86 percent of the implantation sites. By day 3, the transplanted cells were organized as multinucleated fibers containing multiple clusters of nAChRs (N = 2-4), resembling those from non-innervated cultured skeletal muscle fibers. After 7 days, the transplanted cells appeared as a highly vascularized tissue formed by bundles of fibers containing peripheral nuclei. The presence of X chromatin body indicated that subcutaneously developed fibers originated from female donor satellite cells. Differently from the extensor digitorum longus muscle of adult male rat (87.9 ± 1.0 æm; N = 213), the diameter of ectopic fibers (59.1 æm; N = 213) did not obey a Gaussian distribution and had a higher coefficient of variation. After 7 and 14 days, the organization of the nAChR clusters was similar to that of clusters from adult innervated extensor digitorum longus muscle. These findings indicate the histocompatibility of rats from 2BAW colony and that satellite cells transplanted into the subcutaneous space of adult animals are able to develop and fuse to form differentiated skeletal muscle fibers.

X-linked Gene Expression Profiles by RNAi-Mediated BRCA1 Knockdown in MCF7 Cells

Germ-line mutations of the BRCA1 gene confer an increased risk for breast and ovarian cancers. BRCA1 in female cells is directly related with the maintenance of the inactive X chromosome (Xi). The effect by the loss of the BRCA1 function on the X chromosome gene expression remains unclear in cancer cells. We attempted to investigate the expression pattern of the X-linked genes by performing BRCA1 knockdown via RNA interference in the MCF 7 breast cancer cell line. The transcriptional and translational levels of BRCA1 were decreased over 95% in the MCF 7 cells after BRCA1 knockdown. The expression patterns of one hundred ninety X-linked genes were profiled by the X chromosome-specific cDNA arrays. A total of seven percent of the X-linked genes (14/190) were aberrantly expressed by over 2-fold in the MCF7-BRCA1 knockdown cells, which contained two up-regulated genes (2/190, 1%) and 12 downregulated genes (12/190, 6.3%). It is interesting that 72% of the aberrantly expressed X-linked genes were located on the Xq (10/14,) region. Our data suggests that BRCA1 may not be important to maintain X chromosome inactivation in cancer because the BRCA1 knockdown did increase the expression of the only one percent of X-linked genes in the human breast cancer cells.