Patient with Mosaic Turner Syndrome and a Derivative X Chromosome with a Variant Triple X Diagnosis in Fetus: A Case Report.

Although Turner syndrome is most often sporadic, multigenerational recurrence has been reported more often in the offspring of women with mosaic or variant forms of Turner syndrome. We present a case in which natural conception in a woman with identified 45,X/46,XX mosaicism resulted in a fetus with a gain of a derivative X chromosome. The unexpected fetal finding prompted further cytogenetic evaluation of the patient and subsequent identification of an additional cell line with the same derivative X chromosome, not observed in the initial study. To our knowledge, this is the first case in which further investigation of an abnormal noninvasive prenatal screen resulted in the identification of both maternal and fetal sex chromosome abnormality. We discuss the discordant finding, similar cases, and potential phenotype with respect to skewed X inactivation. We also highlight the use of multiple testing methodologies to characterize the serendipitous identification of a derivative X chromosome.

The recurrent TUBB3 Gly98Ser substitution is the first described to inconsistently result in CFEOM3.

Missense variants in TUBB3 have historically been associated with either congenital fibrosis of the extraocular muscles type 3 (CFEOM3) or malformations of cortical development (MCD). Until a recent report identified two amino acid substitutions in four patients that had clinical features of both disorders, pathogenic variants of TUBB3 were thought distinct to either respective disorder. Three recurrent de novo Gly71Arg TUBB3 substitutions and a single patient with a de novo Gly98Ser substitution blurred the MCD and CFEOM3 phenotypic distinctions. Here we report a second patient with a missense c.292G>A (p.Gly98Ser) substitution, but without CFEOM3, the first reported evidence that even the same TUBB3 substitution can produce a spectrum of TUBB3 syndrome phenotypes. Our patient presented with amblyopia, exotropia, optic disc pallor, and developmental delay. Neuroimaging identified hypoplasia of the corpus callosum, interdigitation of the frontal lobe gyri, and dysplasia or hypoplasia of the optic nerves, basal ganglia, brainstem, and cerebellum. This report identifies the TUBB3 Gly98Ser substitution to be recurrent but inconsistently including CFEOM3, and identifies the absence of joint contractures and the presence of optic disc abnormalities that may be genotype-specific to the TUBB3 Gly98Ser substitution.

Breast Cancer and Non-Hodgkin Lymphoma in a Young Male with Cowden Syndrome.

Male breast cancer (MBC) is unusual, especially in young adults. Most cases of MBC as a secondary malignancy relate to the previous treatment with ionizing radiation. MBC can be associated with mutations in hereditary cancer predisposition syndrome genes (i.e., BRCA2); however, no such association has been reported in patients with Cowden syndrome (involving the phosphatase and tensin homolog [PTEN] gene). We describe a patient with Cowden syndrome who was initially diagnosed with B-cell lymphoblastic lymphoma at the age of 7 years, then MBC at the age of 31 years, and never received radiation therapy.

Papillary tumor of the pineal region with synchronous suprasellar focus and novel cytogenetic features.

Papillary tumor of the pineal region (PTPR) is an uncommon neoplasm with variable biologic behavior. Cytogenetic and molecular diagnostic studies are rare, yielding no definitive genetic signature. We report a case of PTPR with a multicentric presentation and unusual cytogenetic features. A 25-year-old man presented with headache, disconjugate gaze, and confusion. Mass lesions in the pineal and suprasellar regions, with identical imaging characteristics, were identified. The former extended partially into the fourth ventricle. It showed typical PTPR histology and losses of chromosomes 3, 7, 10, 14, 18, and Y with gains of chromosomes 3, 8, and 9. Seventeen months postsurgery, the patient is stable without disease progression after radiation therapy. Synchronous mass lesions at presentation and losses of chromosomes 3, 7, 14, 18, and Y are unusual features, adding to the available data and underscoring the biologic and genetic variability associated with these neoplasms.

Cytogenetic abnormalities in follicular dendritic cell sarcoma: report of two cases and literature review.

BACKGROUND: The identification of chromosomal abnormalities in many hematopoietic and mesenchymal neoplasms has contributed significantly to classification systems. Follicular dendritic cell (FDC) sarcoma is an intermediate-grade malignancy with morphological and immunophenotypic features of follicular dendritic cells. Available data on genetic changes in this neoplasm are limited, with only isolated case reports of cytogenetic abnormalities. CASE REPORT: We reviewed histological, immunophenotypic and cytogenetic findings in two cases of FDC sarcoma. The two cases of FDC sarcoma, were observed in female patients, one was nodal and one extranodal and they exhibited relatively complex karyotypes, characterized by structural abnormalities and loss of multiple chromosomes. One patient had several disease recurrences. At the last follow-up both patients were alive with no residual disease. CONCLUSION: The cytogenetic findings in these two cases, coupled with the few previously described abnormal karyotypes, suggest that FDC sarcoma is cytogenetically diverse.

Identification of a novel, recurrent SLC44A1-PRKCA fusion in papillary glioneuronal tumor.

Mixed neuronal-glial tumors are rare and challenging to subclassify. One recently recognized variant, papillary glioneuronal tumor (PGNT), is characterized by prominent pseudopapillary structures and glioneuronal elements. We identified a novel translocation, t(9;17)(q31;q24), as the sole karyotypic anomaly in two PGNTs. A fluorescence in situ hybridization (FISH)-based positional cloning strategy revealed SLC44A1, a member of the choline transporter-like protein family, and PRKCA, a protein kinase C family member of serine/threonine-specific protein kinases, as the 9q31 and 17q24 breakpoint candidate genes, respectively. Reverse transcription-polymerase chain reaction (RT-PCR) analysis using a forward primer from SLC44A1 exon 5 and a reverse primer from PRKCA exon 10 confirmed the presence of a SLC44A1-PRKCA fusion product in both tumors. Sequencing of each chimeric transcript uncovered an identical fusion cDNA junction occurring between SLC44A1 exon 15 and PRKCA exon 9. A dual-color breakpoint-spanning probe set custom-designed for interphase cell recognition of the translocation event identified the fusion in a third PGNT. These results suggest that the t(9;17)(q31;q24) with the resultant novel fusion oncogene SLC44A1-PRKCA is the defining molecular feature of PGNT that may be responsible for its pathogenesis. The FISH and RT-PCR assays developed in this study can serve as valuable diagnostic adjuncts for this rare disease entity.

Pericytoma with t(7;12) and ACTB-GLI1 fusion arising in bone.

Cytogenetic analysis of a primary bone neoplasm with pericytic features in a 67-year-old man revealed a t(7;12)(p22;q13) among other karyotypic abnormalities. Subsequent molecular studies confirmed the presence of an associated ACTB-GLI1 fusion transcript. An identical 7;12 translocation is known to characterize a discrete group of soft tissue tumors belonging to the myopericytic category termed pericytoma with t(7;12). To the best of our knowledge, this is the first case of pericytoma with t(7;12) arising in bone. Cytogenetic and molecular analyses were useful, if not essential, in classifying this rare diagnostic entity.

Translocation t(12;17)(q24.1;q21) as the sole anomaly in a nasal chondromesenchymal hamartoma arising in a patient with pleuropulmonary blastoma.

The identification of recurrent chromosomal abnormalities in benign and malignant mesenchymal neoplasms has provided important pathogenetic insight as well as powerful diagnostic adjuncts. Nasal chondromesenchymal hamartoma (NCMH), an extremely rare benign tumor arising in the sinonasal tract of infants and children, has not been previously subjected to cytogenetic analysis. Histopathologically composed of mixed mesenchymal elements, NCMH exhibits a relatively wide differential diagnosis to include chondromyxoid fibroma, chondroblastoma, aneurysmal bone cyst, fibrous dysplasia, and osteochondromyxoma. An interesting association with pleuropulmonary blastoma has been reported in a small subset of NCMH patients. In the current study, cytogenetic analysis of a NCMH arising in an 11-year-old boy with a past medical history of pleuropulmonary blastoma revealed a novel 12;17 translocation, t(12;17)(q24.1;q21), as the sole anomaly.

Lymphoma cytogenetics.

Lymphomas are a heterogeneous group of neoplasms with distinct morphologic, immunologic, and cytogenetic characteristics. Overlapping morphologic and immunophenotypic features often makes accurate diagnosis difficult. Cytogenetics helps simplify the diagnostic complexities presented in transforming and progressive lymphoid malignancies. Genetic studies using technical advances such as fluorescence in situ hybridization and the newer approaches of array comparative genomic hybridization and gene expression profiling play a critical and often defining role in the diagnosis, progression, prognosis, and therapeutic stratification. This article reviews characteristic cytogenetic abnormalities in specific subtypes of lymphomas at diagnosis, disease progression, and prognosis.

Renal cell carcinoma with novel VCL-ALK fusion: new representative of ALK-associated tumor spectrum.

Renal cell carcinoma represents a model for contemporary classification of solid tumors; however, unusual and unclassifiable cases exist and are not rare in children and young adults. The anaplastic lymphoma kinase (ALK) gene has recently been implicated in subsets of pulmonary, esophageal, breast, and colon cancers. These findings strengthen the importance of molecular classification of carcinomas across different organ sites, especially considering the evolving targeted anticancer therapies with ALK inhibitors. In the current study of six pediatric renal cell carcinomas, two cases exhibited structural karyotypic abnormalities involving the ALK locus on chromosomal band 2p23. Fluorescence in situ hybridization (FISH) studies were positive for an ALK rearrangement in one case, and subsequent 5' rapid amplification of cDNA ends analysis of this tumor revealed that the 3' portion of the ALK transcript encoding for the kinase domain was fused in frame to the 5' portion of vinculin (VCL, NM_003373). The new fusion gene is predicted to have an open reading frame of 4122 bp encoding for a 1374-aa oncoprotein; its expression was shown by immunoblotting with anti-VCL and anti-ALK antibodies in tumor tissue lysates. Immunohistochemistry with the same antibodies demonstrated cytoplasmic and subplasmalemmal localization of the oncoprotein determined by its N-terminal VCL portion. FISH with a custom-designed VCL-ALK dual-fusion probe set confirmed the presence of the fusion in neoplastic cells and demonstrated the potential clinical utility of this approach for detecting VCL-ALK in routinely processed tissue. The five remaining pediatric renal cell carcinomas did not show ALK rearrangement by FISH or ALK expression by immunohistochemistry. The data identify the kidney as a new organ site for ALK-associated carcinomas and VCL as a novel ALK fusion partner. The results should prompt further studies to advance the molecular classification of renal cell carcinoma and help to select patients who would benefit from appropriate targeted therapies.

A novel t(4;22)(q31;q12) produces an EWSR1-SMARCA5 fusion in extraskeletal Ewing sarcoma/primitive neuroectodermal tumor.

Over 90% of Ewing sarcoma/primitive neuroectodermal tumors (PNETs) feature an 11;22 translocation leading to an EWSR1-FLI1 fusion. Less commonly, a member of the ETS-transcription factor family other than FLI1 is fused with EWSR1. In this study, cytogenetic analysis of an extraskeletal Ewing sarcoma/PNET revealed a novel chromosomal translocation t(4;22)(q31;q12) as the sole anomaly. Following confirmation of an EWSR1 rearrangement by the use of EWSR1 breakpoint flanking probes, a fluorescence in situ hybridization positional cloning strategy was used to further narrow the 4q31 breakpoint. These analyses identified the breakpoint within RP11-481K16, a bacterial artificial chromosome (BAC) clone containing two gene candidates FREM and SMARCA5. Subsequent RACE, RT-PCR, and sequencing studies were conducted to further characterize the fusion transcript. An in-frame fusion of the first 7 exons of EWSR1 to the last 19 exons of SMARCA5 was identified. SMARCA5 encodes for hSNF2H, a chromatin-remodeling protein. Analogous to EWSR1-ETS-expressing NIH3T3 cells, NIH3T3 cells expressing EWSR1-hSNF2H exhibited anchorage-independent growth and formed colonies in soft agar, indicating chimeric protein tumorigenic potential. Conversely, expression of EWSR1-hSNF2H in NIH3T3 cells, unlike EWSR1-ETS fusions, did not induce EAT-2 expression. Mapping analysis demonstrated that deletion of the C-terminus (SLIDE or SANT motives) of hSNF2H impaired, and deletion of the SNF2_N domain fully abrogated NIH3T3 cell transformation by EWSR1-SMARCA5. It is proposed that EWSR1-hSNF2H may act as an oncogenic chromatin-remodeling factor and that its expression contributes to Ewing sarcoma/primitive neuroectodermal tumorigenesis. To the best of our knowledge, this is the first description of a fusion between EWSR1 and a chromatin-reorganizing gene in Ewing sarcoma/PNET and thus expands the EWSR1 functional partnership beyond transcription factor and zinc-finger gene families.

C11orf95-MKL2 is the resulting fusion oncogene of t(11;16)(q13;p13) in chondroid lipoma.

Chondroid lipoma, a rare benign adipose tissue tumor, may histologically resemble myxoid liposarcoma or extraskeletal myxoid chondrosarcoma, but is genetically distinct. In this study, an identical reciprocal translocation, t(11;16)(q13;p13), was identified in three chondroid lipomas, a finding consistent with previously isolated reports. A fluorescence in situ hybridization (FISH)-based positional cloning strategy using a series of bacterial artificial chromosome (BAC) probe combinations designed to narrow the 16p13 breakpoint revealed MKL2 as the candidate gene. Subsequent 5' RACE studies demonstrated C11orf95 as the MKL2 fusion gene partner. MKL/myocardin-like 2 (MKL2) encodes myocardin-related transcription factor B in a megakaryoblastic leukemia gene family, and C11orf95 (chromosome 11 open reading frame 95) is a hypothetical protein. Sequencing analysis of reverse transcription-polymerse chain reaction (RT-PCR) generated transcripts from all three chondroid lipomas defined the fusion as occurring between exons 5 and 9 of C11orf95 and MKL2, respectively. Dual-color breakpoint spanning probe sets custom-designed for recognition of the translocation event in interphase cells confirmed the anticipated rearrangements of the C11orf95 and MKL2 loci in all cases. The FISH and RT-PCR assays developed in this study can serve as diagnostic adjuncts for the identification of this novel C11orf95-MKL2 fusion oncogene in chondroid lipoma.

An increased frequency of 13q deletions detected by fluorescence in situ hybridization and its impact on survival in children and adolescents with Burkitt lymphoma: results from the Children's Oncology Group study CCG-5961.

Burkitt lymphoma (BL), an aggressive B-cell malignancy, is often curable with short intensive treatment regiments. Nearly all BLs contain rearrangements of the MYC/8q24 region; however, recent cytogenetic studies suggest that certain secondary chromosomal aberrations in BL correlate with an adverse prognosis. In this multi-centre study, the frequency and impact on clinical outcome of del(13q) and +7 in addition to MYC rearrangements as detected by fluorescence in situ hybridization (FISH) in children and adolescents with intermediate and high-risk BL registered on Children's Cancer Group study CCG-5961 were investigated. Analysis with 13q14.3 and 13q34 loci specific probes demonstrated deletions of 13q in 38/90 (42%) cases. The loss of either 13q14.3 or 13q34 alone occurred in 14% and 8% respectively, while 20% exhibited loss of both regions. Gain of chromosome 7 was observed in 7/68 (10%) cases and MYC rearrangements were detected in 84/90 (93%). Prognostic analysis controlling for known risk factors demonstrated that patients exhibiting loss of 13q, particularly 13q14.3, had a significant decrease in 5-year overall survival (77% vs. 95%, P = 0.012). These observations indicate that del(13q) occurs in childhood BL at frequencies higher than previously detected by classical cytogenetics and underscores the importance of molecular cytogenetics in risk stratification.

Detection of chromosomal aberrations in renal tumors: a comparative study of conventional cytogenetics and virtual karyotyping with single-nucleotide polymorphism microarrays.

CONTEXT: -Renal epithelial neoplasms have characteristic chromosomal imbalances, and we have shown previously that virtual karyotypes derived from single-nucleotide polymorphism microarrays can be performed on formalin-fixed, paraffin-embedded tissue. OBJECTIVE: -To perform a direct comparison of virtual and conventional karyotypes to evaluate concordance of results. DESIGN: -Twenty archival formalin-fixed, paraffin-embedded tumor samples with preexisting, conventional cytogenetic results were analyzed with Affymetrix 10K 2.0 or 250K Nsp single-nucleotide polymorphism microarrays. RESULTS: -Nineteen samples yielded adequate virtual karyotypes for interpretation. Eight samples showed complete agreement between the 2 techniques, and 8 samples showed partial agreement. The disease-defining lesions (eg, loss of 3p for clear cell carcinoma) were identified in all 19 cases by virtual karyotypes and in 15 cases by conventional karyotypes. Virtual and conventional karyotypic findings were concordant in the identification of these disease-defining lesions in 86% (13 of 15) of cases. In 3 cases, virtual karyotypes identified lesions consistent with the morphologic diagnosis, whereas the conventional karyotypes were unsuccessful because of insufficient tumor representation or stromal overgrowth. Two cases with acquired uniparental disomy were identified by single-nucleotide polymorphism arrays, and 5 cases with translocations were identified by conventional karyotype. CONCLUSIONS: -Our results show that both techniques are able to identify the characteristic chromosomal abnormality for renal tumor subtypes in most cases. Discrepancies can be explained by inherent limitations of each technique, inadequate tumor sampling, and tumor heterogeneity. We conclude that virtual karyotyping is a robust alternative to conventional cytogenetics for the evaluation of chromosomal anomalies in formalin-fixed, paraffin-embedded tissues from renal epithelial neoplasms.

Alveolar rhabdomyosarcoma of the head and neck region in older adults: genetic characterization and a review of the literature.

Alveolar rhabdomyosarcoma is remarkably rare in adults older than 45 years. Initial immunoprofiling of a small cell neoplasm of the head and neck region in an older adult may not include myogenic markers. A valuable diagnostic aid and important prognostic parameter in alveolar rhabdomyosarcoma is the identification of PAX3-FOXO1 [t(2;13)(q35;q14)] or PAX7-FOXO1 [t(1;13)(p36;q14)] rearrangements. The purpose of this study was to document the clinicopathologic, immunophenotypic, and genetic features of head/neck alveolar rhabdomyosarcoma in older adults. Prior isolated descriptions of 3 patients were included. Five patients were female and 2 male (median age, 61 years). Each neoplasm was composed of undifferentiated, small round cells in a predominantly solid pattern. Initially, ordered immunostains corresponded with early diagnostic impressions of a hematologic malignancy or neuroendocrine carcinoma. CD56 was positive in 5 of 5 tumors and synaptophysin in 1 of 6. Given the virtual absence of other lymphoid or epithelial markers, muscle immunostains were performed and these were positive. Definitive alveolar rhabdomyosarcoma diagnoses were confirmed genetically. This study illustrates the diagnosis of head/neck alveolar rhabdomyosarcoma in older adults is complicated by its rarity, lack of an alveolar pattern, and a potentially misleading immunoprofile (CD56 and synaptophysin immunoreactivity) if myogenic markers are not used. Both PAX3- and PAX7-FOXO1 alveolar rhabdomyosarcomas were identified in these patients. In children, PAX7-FOXO1 alveolar rhabdomyosarcoma is associated with a significantly longer event-free survival. In contrast, adult alveolar rhabdomyosarcoma behaves more aggressively with a worse overall survival than pediatric alveolar rhabdomyosarcoma. Further follow-up and additional cases are required to assess the prognostic relevance of these fusion transcripts in the context of advanced age.

Characterization of childhood precursor T-lymphoblastic lymphoma by immunophenotyping and fluorescent in situ hybridization: a report from the Children's Oncology Group.

BACKGROUND: T-lymphoblastic lymphoma (T-LBL) accounts for 25-30% of childhood non-Hodgkin's lymphoma and is closely related to T-lymphoblastic leukemia (T-ALL). Recently, we demonstrated distinct differences in gene expression between childhood T-LBL and T-ALL, but molecular pathogenesis and relevant protein expression patterns in T-LBL remain poorly understood. PROCEDURE: Children with T-LBL with disseminated disease were registered and treated on COG protocol 5971. Paraffin-embedded tumor tissue was obtained at diagnosis for immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) studies. We determined the pattern and intensity of staining for c-Myc, Skp2, Mib-1, p53, TCL-1, bcl-2, and bcl-6 proteins by IHC and c-Myc, p53, bcl-2, bcl-6, and TCR alpha/delta molecular alterations by FISH in 22 pediatric T-LBL cases. RESULTS: The majority of T-LBL samples expressed Mib-1 (59%) and c-Myc (77%) proteins in greater than 50% of the cells, but Skp2 (14%), p53 (14%), and bcl-2 (23%) expression was less common. FISH studies demonstrated 18% gains and 10% losses in c-Myc, 16% gains in p53, 12% gains and 6% losses in bcl-2, and 6% gains and 19% losses in bcl-6 with little direct correlation between the IHC and FISH studies. CONCLUSIONS: Childhood T-LBL is a highly proliferative tumor associated with enhanced expression of c-Myc protein, but without detectable c-Myc molecular alterations. FISH studies did not identify consistent etiologies of molecular dysregulation, and future studies with other molecular approaches may be required to elucidate the molecular pathogenesis of childhood T-LBL.

Cytogenetic abnormalities and clinical correlations in peripheral T-cell lymphoma.

Cytogenetic correlations among most types of peripheral T-cell lymphoma (PTCL) have not been very informative to date. This study aimed to identify recurrent chromosomal abnormalities in angioimmunoblastic T-cell lymphoma (AITL), ALK-negative anaplastic large cell lymphoma (ALK-ALCL) and peripheral T-cell lymphoma, unspecified (PTCL-US), and to evaluate their prognostic value. We reviewed the cytogenetic findings of 90 previously-diagnosed cases of PTCL and correlated the cytogenetic findings with the specific histological subtype. The most common abnormalities for AITL were 5q (55%), 21 (41%) and 3q (36%) gains, concurrent trisomies of 5 and 21 (41%), and loss of 6q (23%). In ALK(-) ALCL, gains of 1q (50%) and 3p (30%), and losses of 16pter (50%), 6q13q21 (30%), 15 (30%), 16qter (30%) and 17p13 (30%) were frequent findings. In PTCL-US, frequent gains involved 7q22q31 (33%), 1q (24%), 3p (20%), 5p (20%), and 8q24qter (22%), and losses of 6q22q24 (26%) and 10p13pter (26%). We did not observe any association between specific chromosomal abnormalities and overall survival (OS). However, cases with complex karyotypes, most frequently observed in ALK(-) ALCL and PTCL-US, had a significantly shorter OS. Although, genetic differences were noted in these subtypes, further studies are needed to determine the key pathogenetic events in PTCL.

Gene targeting in adult rhesus macaque fibroblasts.

BACKGROUND: Gene targeting in nonhuman primates has the potential to produce critical animal models for translational studies related to human diseases. Successful gene targeting in fibroblasts followed by somatic cell nuclear transfer (SCNT) has been achieved in several species of large mammals but not yet in primates. Our goal was to establish the protocols necessary to achieve gene targeting in primary culture of adult rhesus macaque fibroblasts as a first step in creating nonhuman primate models of genetic disease using nuclear transfer technology. RESULTS: A primary culture of adult male fibroblasts was transfected with hTERT to overcome senescence and allow long term in vitro manipulations. Successful gene targeting of the HPRT locus in rhesus macaques was achieved by electroporating S-phase synchronized cells with a construct containing a SV40 enhancer. CONCLUSION: The cell lines reported here could be used for the production of null mutant rhesus macaque models of human genetic disease using SCNT technology. In addition, given the close evolutionary relationship and biological similarity between rhesus macaques and humans, the protocols described here may prove useful in the genetic engineering of human somatic cells.

Loss of the PTCH1 gene locus in cardiac fibroma.

BACKGROUND: Cardiac fibroma (CF) is a rare benign tumor that is poorly characterized genetically. CF is more commonly encountered in patients with Gorlin syndrome (3%) than the general population. Mutations of the tumor suppressor gene PTCH1 are the underlying cause of Gorlin syndrome. METHODS: Conventional cytogenetic analysis was performed on a peripheral blood and a CF sample from a 2-week-old male. In addition, fluorescence in situ hybridization (FISH) studies were performed to assess the copy number of the PTCH1 gene locus (9q22.3) on metaphase and interphase cells from these same specimens using yeast artificial protein (YAC) probe 891G1 and on representative paraffin-embedded tissue sections of two additional CFs (one arising in a 2-month-old female and the other in a 13-week-old male). None of the patients had Gorlin syndrome. RESULTS: Karyotypically, the following abnormal chromosomal complement was detected in the 2-week-old male's CF: 46,XY,del(9)(q22q34)[15]. FISH studies revealed homozygous loss of the PTCH1 locus in the cytogenetically analyzed CF and in the CF arising in the 13-week-old male. Heterozygous loss of this locus was identified in the remaining CF from the 2-month-old female. A mutational mechanism other than deletion may be responsible for PTCH1 inactivation on the other locus in this latter patient. Conventional cytogenetic and FISH studies of the peripheral blood sample from the 2-week-old male were normal. CONCLUSION: These data support a tumor suppressor gene role for PTCH1 in nonsyndromic or sporadic CFs.

Lack of a common or characteristic cytogenetic anomaly in solitary fibrous tumor.

Solitary fibrous tumor is a mesenchymal tumor that was initially described as a pleural-based lesion, but later was discovered in many other locations. The light-microscopic appearance of solitary fibrous tumor may overlap with other diagnostic entities; however, consistent tumor cell CD34 immunoreactivity is useful in establishing the diagnosis. Limited data suggest that solitary fibrous tumors are karyotypically diverse, and no common or characteristic anomaly has yet emerged for this entity. Cytogenetic analysis of two solitary fibrous tumors, one peritoneal and the other arising in the liver, revealed predominantly structural abnormalities in the former and numerical imbalances in the latter. Clonal karyotypic abnormalities were lacking in three additional solitary fibrous tumors.