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Biomedical subjects

V Tonk

Publications and source records attributed to V Tonk.

At least 19 recordsLinked to original sources
PubMed2002

Maternal complex chromosome rearrangement ascertained through a del (13)(q12.1q14.1) detected in her mildly affected daughter.

A maternal complex chromosome rearrangement (CCR) involving chromosomes 2, 13, and 20 was ascertained in a normal female through the diagnosis of a deletion of 13q in her daughter. The child has mild clinical features and developmental delay consistent with proximal deletions of 13q that do not extend into band q32 and a del(13)(q12q14.1) that does not involve the retinoblastoma locus by FISH. Maternal studies by GTG banding and FISH showed a complex karyotype with bands 13q12.3-->13q12.1::20p13 translocated to 2p13 and bands 2pter-->2p13::13q12.3-->13q14.1 translocated into band 20p13. This would be the first report of an interstitial deletion of 13q inherited from a parental complex chromosome rearrangement.

Chromosome Deletion↗
PubMed1999

Two distinct forms of the 64,000 Mr protein of the cleavage stimulation factor are expressed in mouse male germ cells.

Polyadenylation in male germ cells differs from that in somatic cells. Many germ cell mRNAs do not contain the canonical AAUAAA in their 3' ends but are efficiently polyadenylated. To determine whether the 64,000 Mr protein of the cleavage stimulation factor (CstF-64) is altered in male germ cells, we examined its expression in mouse testis. In addition to the 64,000 Mr form, we found a related approximately 70,000 Mr protein that is abundant in testis, at low levels in brain, and undetectable in all other tissues examined. Expression of the approximately 70,000 Mr CstF-64 was limited to meiotic spermatocytes and postmeiotic spermatids in testis. In contrast, the 64,000 Mr form was absent from spermatocytes, suggesting that the testis-specific CstF-64 might control expression of meiosis-specific genes. To determine why the 64,000 Mr CstF-64 is not expressed in spermatocytes, we mapped its chromosomal location to the X chromosome in both mouse and human. CstF-64 may, therefore, be absent in spermatocytes because the X chromosome is inactivated during male meiosis. By extension, the testis-specific CstF-64 may be expressed from an autosomal homolog of the X chromosomal gene.

Animals↗
PubMed1998

Characterization of paired tumor and non-tumor cell lines established from patients with breast cancer.

The goal of our study was to develop a panel of tumor cell lines along with paired non-malignant cell lines or strains collected from breast cancers, predominantly primary tumors. From a total of 189 breast tumor samples consisting of 177 primary tumors and 12 metastatic tissues, we established 21 human breast tumor cell lines that included 18 cell lines derived from primary tumors and 3 derived from metastatic lesions. Cell lines included those from patients with germline BRCA1 and FHIT gene mutations and others with possible genetic predisposition. For 19 tumor cell lines, we also established one or more corresponding non-malignant cell strains or B lymphoblastoid (BL) lines, which included 16 BL lines and 7 breast epithelial (2) or stromal (5) cell strains. The present report describes clinical, pathological and molecular information regarding the normal and tumor tissue sources along with relevant personal information and familial medical history. Analysis of the breast tumor cell lines indicated that most of the cell lines had the following features: they were derived from large tumors with or without axillary node metastases; were aneuploid and exhibited a moderate to poorly differentiated phenotype; were estrogen receptor (ER)- and progesterone receptor (PR)-negative; and overexpressed p53 and HER2/neu proteins. Of 13 patients with primary breast cancers receiving curative intent mastectomies, 7 were dead after a mean period of 10 months. Our panel of paired tumor and non-malignant cell lines should provide important new reagents for breast cancer research.

Adult↗
PubMed1998

Translocation (1;22) in refractory anemia and the prognostic significance of karyotypic abnormalities in refractory anemia.

The most common cytogenetic abnormalities associated with myelodysplastic syndromes are deletions of chromosomes 5 and 7 and trisomy 8. Reciprocal translocation is relatively uncommon in refractory anemia. We describe a case of refractory anemia associated with trisomy 8 and a derivative chromosome 22 resulting from t(1;22)(q11;q11.2). The diseases and the role of the various genes that are mapped to these breakpoints are discussed. The prognostic significance of karyotypic abnormalities in refractory anemia are reviewed.

Aged↗
PubMed1998

Characterization of a breast cancer cell line derived from a germ-line BRCA1 mutation carrier.

A tumor cell line, HCC1937, was established from a primary breast carcinoma from a 24-year-old patient with a germ-line BRCA1 mutation. A corresponding B-lymphoblastoid cell line was established from the patient's peripheral blood lymphocytes. BRCA1 analysis revealed that the tumor cell line is homozygous for the BRCA1 5382insC mutation, whereas the patient's lymphocyte DNA is heterozygous for the same mutation, as are at least two other family members' lymphocyte DNA. The tumor cell line is marked by multiple additional genetic changes including a high degree of aneuploidy, an acquired mutation of TP53 with wild-type allele loss, an acquired homozygous deletion of the PTEN gene, and loss of heterozygosity at multiple loci known to be involved in the pathogenesis of breast cancer. Comparison of the primary tumor with the cell line revealed the same BRCA1 mutation and an identical pattern of allele loss at multiple loci, indicating that the cell line had maintained many of the properties of the original tumor. This breast tumor-derived cell line may provide a useful model system for the study of familial breast cancer pathogenesis and for elucidating BRCA1 function and localization.

Adult↗
PubMed1998

Allelotyping demonstrates common and distinct patterns of chromosomal loss in human lung cancer types.

Allelic loss is a hallmark of tumor suppressor gene (TSG) inactivation. We have allelotyped 29 paired lymphoblastoid and lung cancer cell lines derived from 11 patients with small cell (SCLC) and 18 patients with non-small cell lung carcinomas (NSCLC). Statistical analysis indicated that a threshold of 30% separated non-random allelic loss from the random genetic deletions of malignancy. We have identified non-random allelic loss at 42 of 54 (78%) specific chromosomal regions examined, with 22 regions (52%) common between the two major lung cancer histologic types. There were 3 regions (7%) with allelic loss specific for SCLC and 17 regions (41%) specific for NSCLC. Furthermore, there were significant differences in loss of heterozygosity (LOH) frequencies between NSCLC and SCLC at 13 regions on eight chromosome arms (3p, 5q, 6q, 9p, 10q, 11p, 13q, and 19p). Eight homozygous deletions were present in seven cell lines at four regions, 3p12, 3p14.2, 9p21, and 10q23-25. We have also identified novel sites of chromosomal deletions. In particular, there was frequent loss at 11p13 in SCLC and loss at 6p21.3 and 13q12.3 in NSCLC. In this study, we demonstrate that a) non-random allelic losses in lung cancer involve multiple regions; b) some losses are common to both NSCLC and SCLC subtypes, whereas others are subtype specific; c) there are genetic deletions at novel chromosomal regions; and d) several homozygous deletions have been noted. Our studies demonstrate the usefulness of continuous cell lines for detailed allelotyping, for comparing genetic abnormalities between SCLC and NSCLC, and for identifying homozygous deletions.

Adult↗
PubMed1997

Case report: denovo inherited 18p deletion in a mother-fetus pair with extremely variable expression, confirmed by fluorescence in situ hybridization (FISH) analysis.

Denovo deletions of 18p without other associated rearrangement are uncommon. For such a deletion to profoundly affect the fetus of a near normal phenotypic carrier would be rarer. We present such a case in which the chance of a cryptic rearrangement was ruled out by fluorescence in situ hybridization (FISH) analysis. Possible explanations for wide variations in clinical expression are discussed.

Adult↗
PubMed1997

Interphase cytogenetic (in situ hybridization) analysis of astrocytomas using archival, formalin-fixed, paraffin-embedded tissue and nonfluorescent light microscopy.

Astrocytomas contain nonrandom chromosomal abnormalities that recently have been correlated with shortened patient survival. Two frequently reported aberrations are trisomy 7 and monosomy 10. We assessed the numerical complement of chromosomes 7 and 10 in formalin-fixed, paraffin-embedded brain biopsy tissue from 28 diffuse astrocytomas by in situ hybridization using a nonfluorescent enzymatic detection system. Clinical follow-up of at least 5 years was available in 26 cases (93%). Monosomy 10 was identified in 7 cases (25%): astrocytoma, 1 case; anaplastic astrocytoma, 1 case; and glioblastoma, 5 cases. Trisomy 7 was identified in 11 cases (39%): astrocytoma, 5 cases; glioblastoma, 6 cases. Multivariate analysis revealed that monosomy 10 was the most statistically significant negative predictor of patient survival. Numerical chromosomal abnormalities are detectable in astrocytomas in archival tissue using interphase cytogenetics and nonfluorescent light microscopy. Although larger studies are required, our data suggest that potentially useful prognostic information may be obtained with this approach.

Adult↗
PubMed1997

Interstitial deletion of long arm of chromosome no. 5 with growth hormone deficiency--an emerging syndrome?

5p- is a well-defined syndrome, but phenotypic correlations of 5q are poorly described in the literature. We present a case of a female child with interstitial deletion in the 5q13.1q15 region. Comparison of the clinical features of this patient with others reported in the literature suggests an emerging clinical syndrome defined by short stature, failure to thrive, mental retardation, slanting palpebral fissures, malformed ears, short neck and depressed nasal bridge. Based on our endocrine testing, we hypothesize that the short stature could be, in part, due to growth hormone deficiency. The recent assignment of growth hormone receptor gene to the short arm of chromosome 5 and the presence of several genes for growth factors and growth factor receptors on 5q raise interesting possibilities for the explanation of short stature in such cases.

Adult↗
PubMed1997

Del (X)(p21.2) in a mother and two daughters with variable ovarian function.

We report a family in which a woman with the mosaic karyotype 45,X/46,X,del(X)(p21.2) transmitted the deleted X chromosome to two daughters. The nature of the deletion was confirmed by fluorescent in situ hybridization (FISH). All three family members showed somatic Ullrich-Turner syndrome features, but only one daughter had ovarian failure. These observations have implications for the diagnosis of Ullrich-Turner syndrome and genotype/phenotype correlations of X chromosome deletions.

Abnormalities, Multiple↗
PubMed1997

Chromosomal localization of a human mucin gene (MUC8) and cloning of the cDNA corresponding to the carboxy terminus.

A partial cDNA (pAM1) encoding a major airway mucin glycoprotein with novel tandem repetitive sequence has recently been cloned (Shankar, V., M. S. Gilmore, R. C. Elkins, and G. P. Sachdev. 1994. Biochem. J. 300:295-298). In this article, we report additional new sequence derived by 3'-rapid amplification of cDNA ends technique. The sequence corresponds to a stop codon, 3'-untranslated region of 458 bp, a polyadenylation signal, and poly A+ tail, and represents the extreme carboxy terminus of MUC8. A plasmid construct (pAM3) in pBluescript was generated by in-frame ligation of pAM1 to the 479-bp 3'UTR of MUC8. A 5'-end 325-bp fragment of this cDNA subcloned into the protein fusion and expression vector pET28b(+) was used to generate fusion protein under the control of T7 promoter. The purified fusion protein as well as synthetic peptide corresponding to the MUC8 repeat sequence (TSCPRPLQEGTPGS) were used to raise polyclonal antibodies in rabbits. The antiserum to the fusion protein and to the synthetic peptide reacted with the deglycosylated major tracheobronchial mucin. Immunohistochemical studies using the above antibodies localized the MUC8 protein product to submucosal glands in human tracheal epithelium. Furthermore, the gene from which this cDNA is derived, was mapped to chromosome 12 using DNA from a panel of human-mouse somatic cell hybrids. Fluorescence in situ hybridization was used to assign the regional localization to 12q24.3. Since the eight known human mucin genes map to other chromosomes, we have named this gene MUC8, in accordance with mucin gene nomenclature.

Amino Acid Sequence↗
PubMed1996

Robertsonian (15q;15q) translocation in a child with Angelman syndrome: evidence of uniparental disomy.

A balanced Robertsonian translocation 45,XY,t(15q15q) was detected in a patient with mental retardation, microcephaly, and hypertonia. Deletion of the 15q11q13 region was unlikely based on fluorescence in situ hybridization studies that revealed hybridization of appropriate DNA probes to both arms of the Robertsonian chromosome. Inheritance of alleles from 13 highly polymorphic DNA markers on chromosome 15 showed paternal uniparental isodisomy. The clinical, cytogenetic, and molecular results are consistent with a diagnosis of Angelman syndrome.

Angelman Syndrome↗
PubMed1996

Identification and molecular confirmation of a small chromosome 10q duplication [dir dup(10)(q24.2-->q24.3)] inherited from a mother mosaic for the abnormality.

We describe a family in which two siblings exhibited developmental delay, reduced muscle tone and mild muscle weakness. Cytogenetic evaluation demonstrated that both children had a tandem duplication of a small portion of the long arm of chromosome 10 [46,XX or XY,dir dup(10)(q24.2-->q24.3)], inherited from their clinically normal mother, who was found to be mosaic for the duplicated chromosome 10. Fluorescence in situ hybridization approaches, including total chromosome painting and the use of regional specific cosmid probes, were used to confirm the chromosome 10q origin of the duplicated material. This is the smallest confirmed duplication of this portion of chromosome 10 reported to date.

Child↗
PubMed1996

Relapse of precursor B-cell acute lymphoblastic leukemia as an isolated central nervous system mass lesion 9 years after initial diagnosis.

Seven years after completion of chemotherapy for acute lymphoblastic leukemia, diagnosed at the age of 5 years, a black female presented with signs of increased intracranial pressure. Neuroimaging showed a large enhancing extra-axial occipital tumor mass. The resection specimen showed morphologic, cytogenetic, and immunophenotypic features consistent with relapse of the primary leukemia. Bone marrow examination was negative for malignancy. The long duration of complete remission followed by the formation of a mass in the central nervous system are highly unusual features of recurrent acute lymphoblastic leukemia.

Adolescent↗