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F Lonardo

Publications and source records attributed to F Lonardo.

At least 19 recordsLinked to original sources
PubMed2003

Sarcomatoid mesothelioma and its histological mimics: a comparative immunohistochemical study.

AIMS: Differentiating sarcomatoid mesothelioma from other pleural-based spindle cell tumours by light microscopy can be challenging, especially in a biopsy. The role of immunohistochemistry in this differential diagnosis is not as well defined as it is for distinguishing epithelioid mesothelioma from adenocarcinoma. In this study, we investigate the utility of diagnostic immunohistochemistry for distinguishing sarcomatoid mesothelioma from its histological mimics, high-grade sarcoma and pulmonary sarcomatoid carcinoma. METHODS: We stained 20 mesotheliomas with sarcomatoid components (10 biphasic and 10 sarcomatoid mesotheliomas) for pan-cytokeratin, cytokeratin 5/6, calretinin, WT-1, thrombomodulin, and smooth muscle actin. Intensity and distribution of staining were assessed using a semiquantitative scale. Only tumours with unequivocal staining were considered positive for tabulation. We compared the immunophenotypic profiles of these tumours with 24 high-grade sarcomas, 10 pulmonary sarcomatoid carcinomas, and 16 epithelioid mesotheliomas. The sarcomatoid carcinomas were also stained for thyroid transcription factor-1 (TTF-1). RESULTS: Pan-cytokeratin stained 70% of sarcomatoid mesotheliomas, 17% of sarcomas, 90% of sarcomatoid carcinomas, and 100% of epithelioid mesotheliomas. Cytokeratin 5/6 and WT-1 stained most epithelioid mesotheliomas, but rarely stained sarcomas, sarcomatoid carcinomas, or the sarcomatoid components of mesothelioma. Calretinin and thrombomodulin each stained 70% of sarcomatoid mesotheliomas. However, calretinin was also positive in 17% of sarcomas and in 60% of sarcomatoid carcinomas, while thrombomodulin was positive in 38% of sarcomas and in 40% of sarcomatoid carcinomas. Smooth muscle actin was expressed in 60% of sarcomatoid mesotheliomas and in 58% of sarcomas, but in only 10% of sarcomatoid carcinomas. All 10 sarcomatoid carcinomas were negative for TTF-1. CONCLUSIONS: Mesothelioma shows decreased expression of epithelial and mesothelial epitopes in its sarcomatoid components. A wide immunophenotypic overlap exists among sarcomatoid mesotheliomas, sarcoma, and sarcomatoid carcinomas. Cytokeratin and calretinin have the most value in differentiating sarcomatoid mesothelioma from sarcoma. However, because sarcomatoid mesothelioma can occasionally be cytokeratin-negative, the distinction between it and sarcoma may become arbitrary. With the exception of smooth muscle actin, all the markers studied showed similar distributions in sarcomatoid mesothelioma and sarcomatoid carcinoma, including frequent calretinin and thrombomodulin expression in both tumours. Thus, immunohistochemistry plays a more limited role in the differential diagnosis of sarcomatoid tumours compared with epithelioid tumours. For sarcomatoid tumours involving the pleural lining, clinicopathological data, especially information about the gross appearance of the tumour (i.e. localized versus diffuse pleural-based mass), should be noted and carefully correlated with microscopic and immunohistochemical findings.

Biomarkers, Tumor↗
PubMed2001

Multiple high-grade bronchial dysplasia and squamous cell carcinoma: concordant and discordant mutations.

Loss of heterozygosity (LOH) involving chromosomes 3p, 5q, 9p, or 17p and aberrant expression or mutation of p53 are reported previously in selected bronchial dysplasias and squamous cell cancers (SCCs). Yet, comprehensive analyses of LOH patterns at these chromosomal sites and of p53 alterations are not reported for histologically normal bronchial epithelium, high-grade bronchial dysplasia, and SCC present in the same pulmonary resections. Whether concordant or discordant genetic changes are detected in these bronchial tissues, especially when multiple high-grade dysplastic bronchial lesions are present, was studied. Genomic DNA was microdissected from eight pulmonary SCCs and high-grade dysplastic lesions that were associated with SCC. In four cases, two independent high-grade dysplastic bronchial lesions were identified. When available, histologically normal bronchial epithelium was microdissected. Germ-line genomic DNA was isolated from normal lymph nodes. LOH was assessed for 15 microsatellite markers on chromosomes 3p, 5q, 9p, or 17p, sites frequently deleted in lung cancers. Immunohistochemical p53 expression was studied and correlated with p53 DNA sequence analyses. Progressive LOH for these markers was found when SCCs were compared with high-grade dysplasia and histologically normal bronchial epithelium present in the same resections. Histologically normal bronchial specimens had LOH in up to 27% of informative markers. High-grade dysplastic lesions exhibited LOH for 18-45% and SCC had LOH for 18-73% of the markers. Common regions of LOH were found in some dysplasias compared with SCCs. In other dysplasias, discordance was found relative to SCCs, especially for p53 mutations. In cases with a single or second high-grade dysplasia associated with SCC, heterogeneity in LOH markers was detected. These concordant and discordant changes were consistent with convergent and divergent clonal selection pathways in pulmonary squamous cell carcinogenesis. Some histologically normal bronchial epithelial tissues had genetic changes more similar to those in the SCCs than in dysplastic lesions. DNA loss or mutations accumulate in SCC, but discordant genetic changes can exist in the same carcinogen-exposed bronchial tissues. These findings have implications for lung cancer prevention trials.

Bronchial Diseases↗
PubMed2000

A simple method for generating full length cDNA from low abundance partial genomic clones.

BACKGROUND: PCR amplification of target molecules involves sequence specific primers that flank the region to be amplified. While this technique is generally routine, its applicability may not be sufficient to generate a desired target molecule from two separate regions involving intron /exon boundaries. For these situations, the generation of full-length complementary DNAs from two partial genomic clones becomes necessary for the family of low abundance genes. RESULTS: The first approach we used for the isolation of full-length cDNA from two known genomic clones of Hox genes was based on fusion PCR. Here we describe a simple and efficient method of amplification for homeobox D13 (HOXD13) full length cDNA from two partial genomic clones. Specific 5' and 3' untranslated region (UTR) primer pairs and website program (primer3_www.cgv0.2) were key steps involved in this process. CONCLUSIONS: We have devised a simple, rapid and easy method for generating cDNA clone from genomic sequences. The full length HOXD13 clone (1.1 kb) generated with this technique was confirmed by sequence analysis. This simple approach can be utilized to generate full-length cDNA clones from available partial genomic sequences.

Journal Article↗
PubMed2000

Strong association of SYT-SSX fusion type and morphologic epithelial differentiation in synovial sarcoma.

Synovial sarcoma is characterized by a specific recurrent translocation t(X; 18), resulting in either the SYT-SSX1 or SYT-SSX2 gene fusion. Because this is the primary genetic alteration in these tumors, we sought to identify the impact of molecular heterogeneity of the t(X;18) on cell proliferation, apoptosis, and epithelial differentiation in synovial sarcoma. Seventy-three patients with synovial sarcoma (18 biphasic, 55 monophasic) were selected on the basis of availability of tumor material for molecular and immunohistochemical analysis. Tumors were classified as biphasic on the basis of morphologic glandular differentiation. SYT-SSX fusion transcripts were examined by reverse transcriptase polymerase chain reaction using tumor RNA extracted from frozen or paraffin-embedded tissue. Cell proliferation was assessed immunohistochemically by the Ki-67 labeling index. Apoptosis was analyzed immunohistochemically with BAX and BCL2 antibodies and by the TUNEL method. Immunohistochemical evidence of epithelial differentiation was assessed using antibodies to cytokeratins and epithelial membrane antigen. Approximately two thirds of the tumors had an SYT-SSX1 and one third had an SYT-SSX2 fusion transcript. There was a strong association between SYT-SSX fusion type and histologic subtype. All biphasic synovial sarcomas had the SYT-SSX1 fusion, whereas all tumors with SYT-SSX2 were of monophasic morphology. There was, however, no association between SYT-SSX fusion type and expression of cytokeratins and epithelial membrane antigen among monophasic tumors. Tumors with SYT-SSX2 had a significantly higher mean and median Ki-67 labeling index than those with SYT-SSX1, but a comparison of Ki-67 according to fusion type, histologic type, and sample source suggested that the main determinants of proliferation rate were the latter two factors. Specifically, monophasic tumors and metastatic tumors showed significantly higher Ki-67 scores. Apoptosis (by TUNEL) was rarely observed, consistent with prominent expression of the anti-apoptotic protein BCL2 in almost all cases. TUNEL, BCL2, and BAX results did not correlate with SYT-SSX fusion type. These data confirm the strong association of SYT-SSX fusion transcript type with morphologic but not immunophenotypic epithelial differentiation in synovial sarcoma.

Apoptosis↗
PubMed1999

Overexpression of cyclins D1 and E is frequent in bronchial preneoplasia and precedes squamous cell carcinoma development.

Increased protein expression of the G1 cyclins D1 and E is reported in invasive non-small cell lung carcinoma. However, during transformation of the bronchial epithelium, overexpression of these species occurs, and their relationship to aberrant expression of p53 and retinoblastoma (Rb) has not been described previously. To determine the expression of these cell cycle regulators during the development of invasive squamous cell carcinoma (SCC) of the lung, the immunohistochemical expression patterns in normal bronchial epithelium (n = 36), squamous metaplasia (SM; n = 28), and epithelial atypia (n = 34) were compared with that in low-grade dysplasia (LGD; n = 17), high-grade bronchial dysplasia (HGD; n = 30), and SCC (n = 36). Monoclonal anti-p53 Pab1801, polyclonal anti-cyclin D1 DCS6, monoclonal anti-cyclin E HE12, and monoclonal anti-Rb OP-66 antibodies were used. Cyclin D1 was not expressed in normal bronchial epithelium but was detected in 7% of SMs, 15% of atypias; 18% of LGDs, 47% of HGDs, and 42% of SCCs. Cyclin E was not detected in normal epithelium (n = 24), SM (n = 16), or LGD (n = 12), but it was found in 9% of atypias (2 of 22), 33% of HGDs (7 of 21), and 54% of SCCs (13 of 24). p53 was not expressed in normal epithelium, SM, and LGD, but it was overexpressed in 6% of atypias, 53% of HGDs, and 61% of SCCs. Abnormal Rb expression was found only in 2 of 36 cases of SCC. A total of 91% of HGDs and 92% of SCCs exhibited overexpression of at least one of the p53, cyclin D1, or cyclin E species. However, no link was observed between overexpression of p53 and the overexpressed G1 cyclins in preneoplastic lesions. Overexpression of cyclin D1, cyclin E, and p53 occurs frequently and independently in pulmonary SCC and is detected in lesions before the development of invasive carcinoma. In contrast, altered Rb expression is a late and infrequent event in squamous cell carcinogenesis.

Bronchial Diseases↗
PubMed1999

Unknown primary head and neck squamous cell carcinoma: molecular identification of the site of origin.

BACKGROUND: Unknown primary head and neck squamous cell carcinoma (HNSCC) presents as a cervical lymph node metastasis without identification of the primary tumor, despite thorough diagnostic work-up that includes physical examination, computed tomography, esophagoscopy, laryngoscopy, bronchoscopy, and multiple surveillance biopsies. We investigated whether the site of origin of the primary tumor could be localized in the upper aerodigestive tract mucosa by detection of genetic alterations identical to those found in metastatic lesions. METHODS: Microsatellite analysis was performed on metastatic tumors obtained from 18 patients with unknown primary HNSCC. Histologically benign surveillance biopsy specimens were also analyzed. Patients were followed up to 13 years with continuing surveillance for primary mucosal tumors. Most patients were treated with neck dissection followed by radiation therapy to the affected neck and ipsilateral Waldeyer's ring. RESULTS: In 10 (55%) of the 18 patients, at least one histopathologically benign mucosal biopsy specimen from defined anatomic sites (i.e., most likely sites for an occult primary tumor) demonstrated a pattern of genetic alterations identical to that present in cervical lymph node metastases. One patient harboring genetic alterations in the base of the tongue and two patients harboring genetic alterations in a tonsillar fossa subsequently developed HNSCC in the identical or adjacent mucosal region; all three of the primary head and neck mucosal tumors that eventually appeared between 1 and 13 years later in these patients had genetic changes identical to those in the benign mucosal biopsy specimens and in the metastatic lymph nodes. CONCLUSIONS: These data support the hypothesis that histopathologically benign mucosa of the upper aerodigestive tract may harbor foci of clonal, preneoplastic cells that are genetically related to metastatic HNSCC and that such mucosal sites are the sites of origin of unknown primary HNSCC. Microsatellite analysis may represent a clinically useful tool for determining such sites.

Carcinoma, Squamous Cell↗
PubMed1999

Cyclin D1 proteolysis: a retinoid chemoprevention signal in normal, immortalized, and transformed human bronchial epithelial cells.

BACKGROUND: Retinoids (derivatives of vitamin A) are reported to reduce the occurrence of some second primary cancers, including aerodigestive tract tumors. In contrast, beta-carotene does not reduce the occurrence of primary aerodigestive tract cancers. Mechanisms explaining these effective retinoid and ineffective carotenoid chemoprevention results are poorly defined. Recently, the all-trans-retinoic acid (RA)-induced proteolysis of cyclin D1 that leads to the arrest of cells in G1 phase of the cell cycle was described in human bronchial epithelial cells and is a promising candidate for such a mechanism. In this study, we have investigated this proteolysis as a common signal used by carotenoids or receptor-selective and receptor-nonselective retinoids. METHODS: We treated cultured normal human bronchial epithelial cells, immortalized human bronchial epithelial cells (BEAS-2B), and transformed human bronchial epithelial cells (BEAS-2BNNK) with receptor-selective or receptor-nonselective retinoids or with carotenoids and studied the effects on cell proliferation by means of tritiated thymidine incorporation and on cyclin D1 expression by means of immunoblot analysis. We also examined whether calpain inhibitor I, an inhibitor of the 26S proteasome degradation pathway, affected the decline (i.e., proteolysis) of cyclin D1. RESULTS: Receptor-nonselective retinoids were superior to the carotenoids studied in mediating the decline in cyclin D1 expression and in suppressing the growth of bronchial epithelial cells. Retinoids that activated retinoic acid receptor beta or retinoid X receptor pathways preferentially led to a decrease in the amount of cyclin D1 protein and a corresponding decline in growth. The retinoid-mediated degradation of cyclin D1 was blocked by cotreatment with calpain inhibitor I. CONCLUSIONS: Retinoid-dependent cyclin D1 proteolysis is a common chemoprevention signal in normal and neoplastic human bronchial epithelial cells. In contrast, carotenoids did not affect cyclin D1 expression. Thus, the degradation of cyclin D1 is a candidate intermediate marker for effective retinoid-mediated cancer chemoprevention in the aerodigestive tract.

Anticarcinogenic Agents↗
PubMed1999

CDK4 gene amplification in osteosarcoma: reciprocal relationship with INK4A gene alterations and mapping of 12q13 amplicons.

The INK4A gene, localized to human chromosome 9p21, encodes p16INK4A, a tumor suppressor that functions at least in part through the inhibition of CDK4, a cyclin-dependent kinase encoded by a gene at 12q13. To examine INK4A gene alterations in uncultured samples of osteosarcoma and the relationship between INK4A and CDK4 alterations, we analyzed the INK4A and CDK4 genes in 87 specimens from 79 patients. INK4A deletion and CDK4 gene amplification were determined by quantitative Southern blot analysis. INK4A exon 2 was screened for mutation by polymerase chain reaction and single-strand conformational polymorphism analysis. Methylation at the CpG island in INK4A, associated with loss of p16INK4A expression, was assessed by Southern blot analysis using methylation-sensitive restriction enzymes. INK4A deletion (4/55) or rearrangement (1/55) was found in 5 of 55 cases. No INK4A exon 2 point mutations and methylation were detected. CDK4 gene amplification was found in 6 of 67 samples, but not in tumors with INK4A alteration. Amplification analysis of other genes at 12q13 (GLI, CHOP, HMGI-C and MDM2) in these 6 cases supports the view that CDK4 and MDM2 are independent targets for amplification, with variable amplification of the intervening region containing HMGI-C. Of 46 patients studied for both INK4A alterations and CDK4 amplification, the tumors in 22% contained one or the other. The prevalence of these alterations, in conjunction with the reported inactivation of RB in up to 80% of cases, suggests that genetic lesions deregulating the G1 to S cell cycle checkpoint may be an almost constant feature in the pathogenesis of osteosarcoma.

Adolescent↗
PubMed1997

High telomerase activity in primary lung cancers: association with increased cell proliferation rates and advanced pathologic stage.

BACKGROUND: Telomerase enzyme activity is not detected in most normal cells, a phenomenon believed to be associated with limitations on cellular proliferation. Since this activity is detected in nearly all human tumors, including non-small-cell lung cancers, it has been suggested that telomerase activation may be coupled to acquisition of the malignant phenotype. In this study, we determined whether telomerase activity was associated with tumor pathologic stage, tumor cell proliferation rates, and clinical outcome in a cohort of patients with resected non-small-cell lung cancer for whom long-term follow-up was available. METHODS: Primary tumor specimens from 99 patients treated with surgery alone and six patients treated with surgery after chemotherapy were analyzed. Telomerase activity was measured by means of a modified Telomeric Repeat Amplification Protocol (TRAP) assay. Southern blot analysis of terminal restriction fragments was used to evaluate telomere length. Immunohistochemical analysis of Ki-67, a proliferation-associated nuclear antigen, was used to assess tumor cell proliferation. RESULTS: Telomerase activity was detected in 84 of the 99 tumors treated with surgery alone; this activity was not detected in specimens of adjacent, benign lung tissue. Telomerase was detected in only three of six tumors resected after chemotherapy. For the surgery-alone group, statistically significant positive associations were found between the level of telomerase activity and tumor stage, lymph node metastasis, pathologic TNM (tumor-node-metastasis) stage, and Ki-67 immunostaining; a statistically significant inverse association was found between telomerase activity and patient age. No statistically significant differences in telomere length were found in relation telomerase activity or pathologic stage. Telomerase activity was not found to be associated with clinical outcome in a multivariate Cox proportional hazards analysis adjusted for tumor stage and lymph node status. CONCLUSIONS: High telomerase activity is detected frequently in primary non-small-cell lung cancers that exhibit high tumor cell proliferation rates and advanced pathologic stage.

Adenocarcinoma↗
PubMed1997

p53 and MDM2 alterations in osteosarcomas: correlation with clinicopathologic features and proliferative rate.

BACKGROUND: Alterations of the p53 gene and of MDM2, a gene coding for a p53 binding protein, have been implicated in the pathogenesis of osteosarcoma (OS). METHODS: To determine the frequency of alterations of the p53/MDM2 pathway in OS and their possible correlation with clinicopathologic features, MDM2 copy number and p53 protein levels were determined in a series of 83 samples of OS by quantitative Southern blot analysis and immunohistochemistry, respectively. RESULTS: Positivity for p53 was found in 26.5% and MDM2 amplification in 6.6% of the samples analyzed in a mutually exclusive fashion with one exception. Overall, alterations of the p53/MDM2 pathway occurred in 34% of cases; p53 accumulation was not associated with a higher proliferative rate. The mean age of patients with p53 positive OS (40 years) was older than that of the p53 negative group (28 years) (P < 0.04). Furthermore, three of the four cases of OS arising in Paget's disease showed p53 accumulation. CONCLUSIONS: Alterations of the p53/MDM2 pathway are frequent in OS and usually represent mutually exclusive tumorigenic events. p53 does not appear to be a major determinant of proliferative rate in OS.

Adult↗
PubMed1996

Inhibited transformation of immortalized human bronchial epithelial cells by retinoic acid is linked to cyclin E down-regulation.

The retinoids are reported to reduce second primary aerodigestive tract tumors in patients with prior lung or head and neck carcinomas. Yet, the optimal retinoid useful for chemoprevention and those mechanisms linked to this chemoprevention are not identified. This study reports an in vitro model for carcinogen-induced transformation of immortalized human bronchial epithelial (BEAS-2B) cells that was adapted to study the anti-carcinogenic effects of all-trans-retinoic acid (RA). Following exposure to carcinogens: cigarette smoke condensate (CSC) or N-nitrosamine-4-(methylnitrosamino)-1-(3 pyridyl)-1-butanone (NNK), BEAS-2B cells exhibited evidence of transformation. This included an increased anchorage independent growth or acquired ability to form tumors in athymic mice. This transformation was inhibited by RA as demonstrated by a lack of augmented anchorage independent growth or tumor formation in athymic mice for the cells treated with RA. The BEAS-2B cells transformed by NNK exhibited an increase in cyclin E expression which was associated with an increase in the cyclin E-Cdk2 kinase activity. Over-expression of human cyclin E by transfection shows cyclin E enhances the basal clonal growth of BEAS-2B cells. In both the parental and transformed BEAS-2B cells, RA down-regulated cyclin E protein levels which was associated with an inhibition of growth and an accumulation of cells in G1. The data reported here suggest the decline of cyclin E expression represents a potential mechanism for the RA-induced growth suppression which is linked to the anti-carcinogenic effects of RA. Thus, this study reports the adaption of an in vitro model of lung carcinogenesis suitable to test the activity of chemoprevention agents.

Adenoviridae↗
PubMed1996

Novel findings in a patient with Weaver or a Weaver-like syndrome.

We report on a young male patient with an overgrowth syndrome, who had normal birth weight. He had a number of manifestations typical of the Weaver syndrome (WS), such as advanced bone age, peculiar craniofacial appearance, and camptodactyly. He also showed severe mental and speech retardation and demineralisation of the bones of the hands and feet. The latter can be considered as unreported manifestations of WS, or the patient could represent an example of a new WS-like syndrome.

Abnormalities, Multiple↗
PubMed1996

Microadenocarcinoma of the pancreas--morphologic pattern or pathologic entity? A reevaluation of the original series.

The term microadenocarcinoma was first proposed for a subtype of pancreatic carcinoma by Cubilla and Fitzgerald in 1975 based largely on the morphological features of 15 cases. Since that time, no independent studies have appeared in the English literature to address whether microadenocarcinoma represents a distinctive tumor or a pattern of growth, and some authors have questioned its existence as a definable entity. Immunohisto-chemistry is now available to allow the identification of lines of differentiation in pancreatic neoplasms, on which their classification is largely based. Reasoning that heterogeneity of differentiation between different cases would not justify the separation of microadenocarcinomas from other better defined pancreatic neoplasms, we reevaluated 12 cases from the original series using antibodies for acinar, endocrine, and ductal differ-entiation. Two distinctive morphological patterns were identified: microglandular and solid cribriform. The microglandular cases (n = 6) were not separable from typical ductal adenocarcinomas either morphologically or immunophenotypically. Of the solid-cribriform cases (n = 6), immunohistochemistry revealed three to be acinar cell carcinomas, one an endocrine carcinoma, one a mixed endocrine-ductal carcinoma, and one a ductal adenocarcinoma. We concluded that with the benefit of further study, most of these cases could be reclassified as other types of pancreatic carcinoma. Microadenocarcinoma is best regarded as a pattern of growth associated with an aggressive clinical course rather than a distinctive entity.

Adult↗
PubMed1995

Molecular diagnosis of synovial sarcoma and characterization of a variant SYT-SSX2 fusion transcript.

The translocation t(X;18)(p11;q11) is seen in > 80% of synovial sarcomas (SS) with informative karyotypes. The breakpoints of the t(X;18) have been cloned and shown to involve two novel genes, SSX (at Xp11) and SYT (at 18q11), which produce a chimeric SYT-SSX transcript as a result of the translocation. Recently, SSX has been shown to be duplicated, with both copies, SSX1 and SSX2, located within distinct subregions of Xp11. We performed a reverse transcriptase polymerase chain reaction (RT-PCR) assay for both chimeric SYT-SSX transcripts in a series of 35 SS (29 monophasic, 6 biphasic) to assess its usefulness in molecular diagnosis and to evaluate the incidence of molecular variants. Of the 35 cases, 29 (83%) showed a specific SYT-SSX RT-PCR product, using a consensus primer for SSX1 and SSX2 Upon excluding three negative cases that had poor quality RNA, the proportion of positives rose to 91% (29/32). The 29 positive cases were further studied using primers specific for either SSX1 or SSX2; 19 cases were positive for SYT-SSX1 and 10 for SYT-SSX2. The relationship of histological subtype (monophasic versus biphasic) to SSX1 or SSX2 involvement was not statistically significant. In a single histologically unremarkable monophasic SS, a slightly larger SYT-SSX2 RT-PCR product was observed. Sequencing of this novel variant showed a 129-bp segment inserted between the usual SYT and SSX2 fusion points, of which 126 bp were derived from a more proximal (5') portion of SSX2 The 3 bp immediately 5' to the fusion point could not be assigned to either SYT or SSX2 and may represent an insertion-deletion or a cryptic splicing event. This fragment maintains the reading frame of the chimeric product and encodes a predicted protein larger by 43 amino acids, which nevertheless replaces the region homologous to the transcriptional repression domain Kruppel-associated box, recently recognized in the 5' portion of the SSX genes, with all but the 3' end of the SYT transcript. Thus, a diagnosis of SS may be confirmed in > 90% of cases using RT-PCR detection of the chimeric transcript resulting from the t(X;18), and the incidence of molecular variants appears low.

Adolescent↗
PubMed1994

Prenatal sonographic diagnosis of non-rhizomelic chondrodysplasia punctata.

BACKGROUND: Chondrodysplasia punctata is a rare heterogeneous group of bone dysplasias occurring with an incidence of one in 100,000 live births. Prenatal sonographic diagnosis of non-rhizomelic chondrodysplasia punctata (Conradi-Hünermann syndrome) has previously been reported only following detection of overall limb shortening. CASE: Multiple sonographic skeletal findings of premature epiphyseal calcifications, other unusual calcifications, kyphoscoliosis, and asymmetrical limb shortening, typical of non-rhizomelic chondrodysplasia punctata, led to second-trimester prenatal sonographic diagnosis of this condition. CONCLUSION: Second-trimester prenatal sonographic diagnosis of premature epiphyseal calcifications associated with non-rhizomelic chondrodysplasia punctata is possible.

Adult↗