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J Limon

Publications and source records attributed to J Limon.

At least 19 recordsLinked to original sources
PubMed2006

Germline MSH2 and MLH1 mutational spectrum including large rearrangements in HNPCC families from Poland (update study).

Germline mutations in the DNA mismatch repair genes MSH2 and MLH1 account for a significant proportion of hereditary non-polyposis colorectal cancer (HNPCC) families. One approach by which development of an efficient DNA-testing procedure can be implemented is to describe the nature and frequency of common mutations in particular ethnic groups. Two hundred and twenty-six patients from families matching the Amsterdam II diagnostic criteria or suspected HNPCC criteria were screened for MSH2 and MLH1 germline mutations. Fifty different pathogenic mutations were found, 25 in MSH2 and 25 in MLH1. Twenty-four of these had not previously been described in other populations. Among our 78 families with MSH2 or MLH1 mutations, 54 (69.2%) were affected by recurrent mutations including 38 found at least twice in our own series. Two of the most frequent alterations were a substitution of A to T at the splice donor site of intron 5 of MSH2 and a missense change (A681T) of MLH1 found in 10 and eight families, respectively. Among large deletions detected by the multiplex ligation-dependent probe amplification assay, exon 9 deletions in the MSH2 gene were found in two families. Our results indicate that a screening protocol specific for the Polish population that is limited to the detection of all reported mutations will result in the identification of the majority of changes present in MLH1 and MSH2 genes in Polish HNPCC kindreds.

Adaptor Proteins, Signal Transducing↗
PubMed2005

Root morphology of mandibular premolars in 40 patients with Turner syndrome.

AIM: To analyse root morphology of mandibular premolars in 40 females with Turner syndrome. METHODOLOGY: All patients aged 18-50 years (mean+/-SD: 26.2+/-6.22) were clinically and cytogenetically diagnosed and divided into three groups according to karyotype: I-with 45,X (n=19); II-with 46,X,i(Xq) and other structural changes of this chromosome (n=8); III-with mos45,X/46,XX and other mosaic karyotype (n=13). The control group consisted of 30 healthy women aged 20-50 years (mean+/-SD: 31.52+/-5.21) who underwent dental treatment at the Department of Conservative Dentistry and Department of Periodontology and Oral Mucosa Diseases, Medical University of Gdańsk, Poland. The root morphology of mandibular premolars was studied based on orthopantomogram X-ray images. The results were analysed using chi-square test with Yates's adjustment. RESULTS: Separate mesial and distal root canals and separate root apices were noted on orthopantomograms in patients with Turner syndrome. Two-rooted mandibular first premolars were observed in 34% of cases in group 45,X (group I), in 31% of cases in the group with structural aberrations of chromosome X (group II) and in 31% of cases with mosaic karyotypes (group III). Two-rooted mandibular second premolars were observed in 39% cases in group 45,X and in 31% of cases in the group with structural aberrations of chromosome X and in 35% of cases with mosaic karyotypes. This type of root morphology was not observed in the control group. No significant difference was found between the three groups of Turner syndrome. CONCLUSION: Highly significant differences in root morphology of mandibular premolars between patients with Turner syndrome and a population control group were found.

Adolescent↗
PubMed2004

A novel c.C2754 > T transition in the androgen receptor gene introduces the premature termination codon Q798X and results in a truncated form of the receptor.

A genetic analysis of a female with a 46,XY genotype and typical symptoms of the complete androgen insensitivity syndrome (CAIS) was conducted. The patient was diagnosed with an abdominal tumor due to the presence of a Sertoli cell adenoma in both gonads. Multiple temperature single-stranded conformational polymorphism (MSSCP) and sequence analyses of the androgen receptor gene revealed a c.C2754 > T mutation in exon 6. This mutation, which has not been previously reported, alters a Gln codon to a termination codon (Q798X). This results in the interruption of the amino acid sequence of the androgen receptor within the ligand-binding domain between helices VII and VIII. The truncated form of the receptor is devoid of 123 amino acids at the carboxyl end, a major part of the ligand-binding domain, and the AT2 sequence responsible for the activation of the transcription. It was concluded that the novel c.C2754 > T transition rendered the androgen receptor incapable of both ligand binding and activating the transcription, and was the cause of CAIS in the patient.

Adenoma↗
PubMed2001

Clinical and molecular-cytogenetic studies in seven patients with ring chromosome 18.

We report the results of detailed clinical and molecular-cytogenetic studies in seven patients with ring chromosome 18. Classical cytogenetics and fluorescence in situ hybridization (FISH) analysis with the chromosome 18 painting probe identified five non-mosaic and two complex mosaic 46,XX,dup(18)(p11.2)/47,XX,dup(18)(p11.2),+r(18) and 46,XX,dup(18)(p11.32)/47,XX,dup(18)(p11.32),+r(18) cases. FISH analysis was performed for precise characterization of the chromosome 18 breakpoints using chromosome 18-specific short-arm paint, centromeric, subtelomeric, and a panel of fifteen Alu- and DOP-PCR YAC probes. The breakpoints were assessed with an average resolution of approximately 2.2 Mb. In all r(18) chromosomes, the 18q terminal deletions ranging from 18q21.2 to 18q22.3 ( approximately 35 and 9 Mb, respectively) were found, whereas only in four cases could the loss of 18p material be demonstrated. In two cases the dup(18) chromosomes were identified as inv dup(18)(qter-->p11.32::q21.3-->qter) and inv dup(18)(qter-->p11.32::p11.32-->p11.1: :q21.3-->qter)pat, with no evidence of an 18p deletion. A novel inter-intrachromatid mechanism of formation of duplications and ring chromosomes is proposed. Although the effect of "ring instability syndrome" cannot be excluded, the phenotypes of our patients with characteristic features of 18q- and 18p- syndromes are compared and correlated with the analyzed genotypes. It has been observed that a short neck with absence of cardiac anomalies may be related to the deletion of the 18p material from the r(18) chromosome.

Abnormalities, Multiple↗
PubMed2001

Mutations in the EDA gene in three unrelated families reveal no apparent correlation between phenotype and genotype in the patients with an X-linked anhidrotic ectodermal dysplasia.

Anhidrotic ectodermal dysplasia (EDA) is caused by mutations in the EDA gene encoding ectodysplasin A, a member of the TNF ligand superfamily involved in the communication between the cells. The structure of the EDA gene was investigated in three patients exhibiting clinical symptoms of EDA in an attempt to correlate the molecular findings with the phenotype of the patients. Genomic DNA was analyzed by single stranded conformation polymorphism (SSCP) followed by direct sequencing. In one of the patients, as well as in his heterozygous mother and sister, a single T insertion was evidenced in exon 3 between nucleotides 713 and 714 that changed Lys codon (AAA) into a termination codon TAA (Lys158Ter). In the other patient, A1321T transversion was demonstrated. The same mutation was found in his heterozygous mother and resulted in a change of Ileu360Asn that might generate an additional glycosylation site. In the third patient an A1285G transition was revealed. This mutation that originated de novo was localized in a region that is highly conserved in TNF ligand family and caused substitution of Ala349Thr. Localization of the mutations in the extracellular domain of ectodysplasin A suggested that the primary cause of EDA is a defect in communication between the cells responsible for the development of skin appendages. Despite a different character and localization of the mutations, no apparent correlation between phenotype and genotype of the patients was evidenced. Some differences in the patients' phenotype were observed.

Child↗
PubMed2001

Spectral karyotyping reveals 17;22 fusions in a cytogenetically atypical dermatofibrosarcoma protuberans with a large marker chromosome as a sole abnormality.

The presence of an extra ring chromosome containing material from 17q and 22q, or, less frequently, a t(17;22)(q22;q13), is a cytogenetic hallmark of dermatofibrosarcoma protuberans (DFSP). However, occasionally tumors with other, atypical karyotypes are encountered. We describe a case of recurrent DFSP without a ring chromosome or a t(17;22) on standard cytogenetic analysis. In all cells analyzed by G-banding, an additional, large marker chromosome was present as a sole abnormality. This chromosome apparently included chromosome 8 or the 8q arm, but the origin of its remaining part could not be determined with certainty. To characterize further the abnormal chromosome, we applied spectral karyotyping (SKY). SKY confirmed the presence of an extra chromosome 8 or arm 8q in the marker and showed that its remaining part was composed of segments from chromosomes 7, 17, 21, and 22, with two copies of a 17;22 fusion. Our results and the literature data suggest that, in addition to a specific 17;22 fusion, amplification of material from chromosomes 17, 22, 8, 5, 7, and 21 may play a role in DFSP development and/or progression. Furthermore, our case demonstrates the usefulness of SKY in detection of a diagnostically relevant 17;22 fusion in DFSP patients who have unusual karyotypic features.

Adult↗
PubMed2001

Clinical impact of molecular and cytogenetic findings in synovial sarcoma.

Synovial sarcoma is an aggressive soft-tissue tumor that accounts for up to 10% of soft-tissue sarcomas. Cytogenetically, synovial sarcoma is characterized by the t(X;18)(p11;q11), found in more than 95% of the tumors. This translocation results in rearrangements of the SYT gene in 18q11 and one of the SSX1, SSX2, or SSX4 genes in Xp11, creating a SYT/SSX1, SYT/SSX2, or SYT/SSX4 chimeric gene. It has been shown that patients with SYT/SSX1 fusion genes have a shorter metastasis-free survival than do patients with SYT/SSX2. Previous studies have also suggested that clonal evolution may be associated with disease progression. In the present study, RT-PCR analysis showed that all 64 examined synovial sarcomas from 54 patients had SYT-SSX chimeric genes. SYT/SSX1 was found in 40 tumors from 33 patients, SYT/SSX2 in 23 tumors from 20 patients, and SYT/SSX4 in one case. Two patients had variant SYT/SSX2 transcripts, with 57 bp and 141 bp inserts, respectively, between the known SYT and SSX2 sequences. Patients with tumors with SYT/SSX1 fusions had a higher risk of developing metastases compared to those with SYT/SSX2 fusions (P = 0.01). The reciprocal transcripts SSX1/SYT and SSX2/SYT were detected using nested PCR in 11 of the 40 samples with SYT/SSX1 and 5 of the 23 samples with SYT/SSX2, respectively. Among 20 blood samples, SYT/SSX1 and SYT/SSX2 were detected in one sample each. The t(X;18), or variants thereof, was found cytogenetically in all patients but three. Among 32 primary tumors, the t(X;18) or a variant translocation was the sole anomaly in 10. In contrast, of the seven metastatic lesions that were investigated prior to radiotherapy, only one had a t(X;18) as the sole anomaly; all other tumors displayed complex karyotypes. Cytogenetic complexity in primary tumors was, however, not associated with the development of metastases. Tumors with SYT/SSX2 less often (4/12 vs. 7/15) showed complex karyotypes than did tumors with SYT/SSX1, but the difference was not significant. Combining cytogenetic complexity and transcript data, we found that the subgroup of patients with tumors showing simple karyotypes and SYT/SSX2 fusion had the best clinical outcome (2/8 patients developed metastases), and those with tumors showing complex karyotypes together with SYT/SSX1 fusion the worst (6/7 patients developed metastases). This corresponded to 5-year metastasis-free survival rates of 0.58 and 0.0, respectively (P = 0.02).

Adolescent↗
PubMed2001

Novel RB1 gene constitutional mutations found in Polish patients with familial and/or bilateral retinoblastoma.

Retinoblastoma is the most common intraocular malignancy in children. It is estimated that 60 percent of cases are nonhereditary and unilateral, 15% are hereditary and unilateral, and 25 percent are hereditary and bilateral. Hereditary predisposition for retinoblastoma is caused by germline mutations in the RB1 gene and is transmitted in an autosomal dominant manner. Most of the reported mutations are unique to one family, but there are sites where mutations are recurrent. We have performed RB1 gene mutation analysis in eight patients with familial and/or bilateral retinoblastoma by DNA/RNA sequencing. Constitutional mutations were found in five out of eight patients. Three mutations were novel: g.IVS7+5G>A, g.156709T>A, and g.IVS21+1G>A (p.G203-E240del, p.Y659X, and p.I703-E737del).

Base Sequence↗
PubMed2001

Calretinin and other mesothelioma markers in synovial sarcoma: analysis of antigenic similarities and differences with malignant mesothelioma.

Synovial sarcoma (SS) is a mesenchymal neoplasm that typically shows epithelial differentiation. SS commonly metastasizes to lung and pleura, and has also been reported as the primary in these locations. The histologic distinction of SS from mesothelioma may be difficult because of the combination of epithelioid and spindle cells, potentially shared locations, and antigenic expression. In this study the authors examined 103 well-documented SSs including 41 biphasic, 44 monophasic, and 18 poorly differentiated SSs in comparison with 23 epithelioid and seven sarcomatous mesotheliomas. Most biphasic SSs (29 of 41, 71%) had fields or foci of calretinin-positive tumor cells. The spindle cell components were more often positive (55%), whereas 14% of tumors had positive epithelial cells. The monophasic and poorly differentiated SSs commonly had foci of calretinin-positive cells (in 52% and 56% of cases respectively). In comparison, all 23 epithelioid mesotheliomas (EM) were extensively calretinin positive and seven sarcomatoid mesotheliomas were variably calretinin positive. HBME-1 positivity was similarly detected in biphasic SS and EM (100% and 87% respectively). Among the other sarcomas, two of 15 malignant peripheral nerve sheath tumors were focally calretinin positive, whereas 16 epithelioid sarcomas, 20 leiomyosarcomas, 20 gastrointestinal stromal tumors, and 20 angiosarcomas were negative. Biphasic SSs differed from mesotheliomas by their more common BerEp4 positivity (90%) whereas EMs showed focal reactivity in 13% cases. Marked CD15 reactivity was rare in both. Wilms tumor protein-1 (WT1) was not detected in SS, but was present in 12 of 17 EMs. CD141 was rare in SS, limited to spindle cell components, whereas EMs typically showed prominent membrane staining in epithelial cells. Simple epithelial keratins were present in all epithelial cells of biphasic SS and mesothelioma (keratin 7[K7], K19), but were only focal in monophasic and poorly differentiated SS. Biphasic SSs were extensively K14 positive (89% of cases), whereas epithelial and sarcomatoid mesotheliomas typically showed only scattered positive cells. The potentially shared calretinin patterns in SS and mesothelioma require the use of other markers. The discriminating features include extensive BerEp4 positivity, rarity of CD141, and lack of WT1 in SS. Global expression of K7 and K19 in mesotheliomas versus focal expression in monophasic and poorly differentiated SSs, and differential patterns of K14 expression may also be helpful.

Adolescent↗
PubMed2001

Influence of diethylenetriamine (DETA) and sodium nitroprusside (NaNP) on sister chromatid exchange frequency and cell kinetics in cultured human lymphocytes.

Diethylenetriamine (DETA) and Sodium Nitroprusside (NaNP), the exogenous NO-generating compounds, were tested for their genotoxicity in human lymphocytes in vitro using the sister chromatid exchange (SCE) technique. Both compounds were found to be inactive in inducing SCE in concentrations from 0.3 to 30 pM. However both compounds displayed an inhibiting effect on cell kinetics.

Journal Article↗
PubMed2000

Cytogenetics of hepatoblastoma: further characterization of 1q rearrangements by fluorescence in situ hybridization: an international collaborative study.

BACKGROUND: Hepatoblastoma (HBT) is the most common hepatic neoplasm in children. This notwithstanding, little is known about pathogenetic factors, such as genetic abnormalities, of importance for the development and progression of this tumor type. To date, only 33 cytogenetically abnormal HBT have been published, and trisomies for chromosomes 2 and 20 have been shown to be the most frequent aberrations. Recently, unbalanced translocations involving proximal 1q have been described in several HBT, suggesting that a pathogenetically important gene maps to 1q. PROCEDURE: Six primary and one recurrent HBT were cytogenetically analyzed after short-term tissue culture. In addition, fluorescence in situ hybridization (FISH) studies, using locus-specific probes, were performed on three of these pediatric HBT as well as on one previously reported adult HBT. RESULTS: Total or partial trisomy 8, gain of chromosome 20, and structural rearrangements of chromosome 1 were detected in three HBT, and overrepresentation of chromosome 2 material was found in two HBT. The adjacent chromosome bands 1q12 and 1q21 were involved in three translocations, t(1;2), t(1;4), and t(1;11), which were all unbalanced and resulted in gain of 1q material. The previously reported adult HBT displayed 1q deletions with breakpoints at 1q12-21. FISH analyses of the 1q rearrangements revealed that all breakpoints were within the heterochromatic region. CONCLUSIONS: These findings provide further support for the importance of trisomies 2, 8, and 20 and rearrangements of 1q in the development of HBT. Furthermore, the consistent localization of breakpoints within the heterochromatic segment of chromosome 1 suggests that the important pathogenetic consequence of 1q abnormalities is the resulting genomic imbalance rather than a specific gene rearrangement.

Child, Preschool↗
PubMed2000

Founder BRCA1 mutations and two novel germline BRCA2 mutations in breast and/or ovarian cancer families from North-Eastern Poland.

Germline mutations in the BRCA1 and BRCA2 genes account for the majority of high-risk breast/ovarian cancer families, depending on the population studied. Previously, BRCA1 mutations were described in women from Western Poland. To further characterize the spectrum of BRCA1 mutations and the impact of BRCA2 mutations in Poland, we have analyzed 25 high-risk breast and/or ovarian cancer families from North-Eastern Poland for mutations in all coding exons of the BRCA1 and BRCA2 genes, using combined heteroduplex analysis/SSCP followed by direct DNA sequence analysis. Out of 25 probands a total of five (20%) carried three recurrent BRCA1 mutations (300T>G, 3819del5, 5382insC). The 300T>G mutation accounted for 60% (3/5) of BRCA1 mutations and allelotyping suggested a common founder of this mutation. No unique mutations were found. In addition, we identified three BRCA2 (12%) mutations, one recurrent 4075delGT, and two novel frameshift mutations, 7327ins/dupl19 and 9068delA. We conclude that 30% of high-risk families from North-Eastern Poland may be due to recurrent BRCA1 and unique BRCA2 mutations. Intriguingly, the BRCA1 mutation spectrum seems to be different within subregions of Poland.

Adult↗
PubMed2000

Patterns of keratin polypeptides in 110 biphasic, monophasic, and poorly differentiated synovial sarcomas.

Synovial sarcoma is a mesenchymal neoplasm of unknown histogenesis that shows various degrees of epithelial differentiation. It is known to contain simple epithelial keratins, and the possibility of complex epithelial keratin expression has been suggested. In this study, we immunohistochemically examined 110 well-documented synovial sarcomas including 44 biphasic, 48 monophasic, and 18 poorly differentiated (undifferentiated, highly mitotically active) tumors for 11 different keratin (K) polypeptides of the Moll catalogue. The epithelia of biphasic synovial sarcomas showed consistent, extensive reactivity for K7, K8, K14, K18, and K19. Other keratins seen in the epithelia of biphasic tumors included K17 (variable, in 77%), K13 (25%), K16 (23%), and K6 (24%) in the minority of biphasic tumors, predominantly in stratified-appearing epithelia. K10 was detected only focally in one case that showed keratinizing squamous differentiation. Focal expression of K20 was seen in 27% of cases. Monophasic synovial sarcomas had a more limited keratin repertory. Simple epithelial keratin positivity was detected, usually focally for K7 (79%), K19 (60%), K8 (45%), and K18 (46%). Two cases showed more extensive keratin positivity in the spindle cells. The monophasic tumors showed limited positivity for complex epithelial keratins: K14 (28%) and K17 (10%). K20 was detected focally in 6% of the monophasic tumors; other keratins were not detected. The poorly differentiated synovial sarcomas showed limited simple epithelial keratin reactivity, usually limited to scattered cells: K19 (61%), K7 (50%), K18 (47%), K8 (33%), but five cases showed more extensive positivity. Complex epithelial keratins were scant: K14 in one case and K17 in two cases. The immunoreactivity of capillary endothelia seen for K7 and K18 (but not for K8 and K19 with the antibodies used) is a potential diagnostic pitfall, and may cause overdiagnosis of synovial sarcoma if not properly recognized. In summary, we show complex patterns of keratins in synovial sarcoma, especially in the biphasic tumors. Such patterns establish a baseline in differential diagnostic considerations, and give an insight into the complex epithelial differentiation of this enigmatic mesenchymal tumor.

Adolescent↗
PubMed2000

A case with 47,XXY,del(11)(q23) karotype-coexistence of Jacobsen and Klinefelter syndromes.

A case with 47,XXY, del(11)(q23) karyotype-coexistence of Jacobsen and Klinefelter syndromes: A two-year-old dysmorphic male child was found to have 47,XXY,del(11)(q23) karyotype. Domination of the clinical features of Jacobsen syndrome was observed: mild mental retardation, trigonocephaly, ptosis, downward slanting palpebral fissures, low set ears, carp-shape mouth and micrognathia. Transient thrombocytopenia and leukopenia were also present. Over the following five years gynecomastia and eunuchoid body proportions became evident as clinical features of Klinefelter syndrome. This is the first description of the coexistence of both syndromes.

Brain↗