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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The ret/PTC oncogene, rearranged form of the ret proto-oncogene (c-ret), has been detected specifically in a minority of papillary thyroid carcinomas. Three forms of the ret/PTC oncogene have been identified; the two most common forms, ret/PTC-1 and ret/PTC-3, both result from a paracentric inversion, of the long arm of chromosome 10. In this study, we have successfully amplified the chimeric introns resulting from these inversions, ranging from 1.4 to 10 kb, from four of five tumors known to contain the ret/PTC-1 oncogene (where c-ret rearranges with the H4 gene), and from 1/1 tumors containing the ret/PTC-3 oncogene (where c-ret rearranges with the ele1 gene). We localized the breakpoints within the chimeric introns using nested PCR, and determined the exact nucleotide sequence at the breakpoint for each tumor. Our results indicate that the breakpoints in c-ret occur at sites distributed across intron 11, where breaks in H4 intron 1 appear more frequently at the 5'- end of the intron. Interestingly, in all tumors that we investigated, the breakpoints occurred at sits of two or three nucleotide matches between the contributing germline sequences. In summary, we describe a simple, convenient way to investigate the ret/PTC breakpoints, and have revealed several common features of the breakpoints which warrant further investigations.
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PMID:Breakpoint characterization of the ret/PTC oncogene in human papillary thyroid carcinoma. 863 4

The basal cell nevus syndrome (BCNS) is characterized by developmental abnormalities and by the postnatal occurrence of cancers, especially basal cell carcinomas (BCCs), the most common human cancer. Heritable mutations in BCNS patients and a somatic mutation in a sporadic BCC were identified in a human homolog of the Drosophila patched (ptc) gene. The ptc gene encodes a transmembrane protein that in Drosophila acts in opposition to the Hedgehog signaling protein, controlling cell fates, patterning, and growth in numerous tissues. The human PTC gene appears to be crucial for proper embryonic development and for tumor suppression.
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PMID:Human homolog of patched, a candidate gene for the basal cell nevus syndrome. 865 45

The nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder characterized by multiple basal cell carcinomas (BCCs), pits of the palms and soles, jaw keratocysts, a variety of other tumors, and developmental abnormalities. NBCCS maps to chromosome 9q22.3. Familial and sporadic BCCs display loss of heterozygosity in this region, consistent with the gene being a tumor suppressor. A human sequence (PTC) with strong homology to the Drosophila segment polarity gene, patched, was isolated from a YAC and cosmid contig of the NBCCS region. Mutation analysis revealed alterations of PTC in NBCCS patients and in related tumors. We propose that a reduction in expression of the patched gene can lead to the developmental abnormalities observed in the syndrome and that complete loss of patched function contributes to transformation of certain cell types.
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PMID:Mutations of the human homolog of Drosophila patched in the nevoid basal cell carcinoma syndrome. 868 79

The receptor tyrosine kinase proto-RET is believed to contribute to thyroid oncogenesis by activation of its tyrosine kinase either by point mutation or rearrangement. The papillary thyroid cancer cell lines PTC-1113A, L, and R were established from a recurrent thyroid cancer and its metastases. The rearrangement of the proto-ret oncogene in the cell line PTC-1113A is demonstrated by Southern analysis utilizing the probe for rearranged ret that encodes the fusion protein H4/tyrosine kinase. In contrast, rearranged ret alleles were not found in the cell lines that developed from metastases, nor in DNA isolated from the recurrent tumor. The cell line PTC-1113A may represent a population of tumor cells that gained a growth advantage due to rearranged ret. This is the second human thyroid cancer cell line harboring rearranged ret, and may serve to study the function of ret activation in thyroid cancers.
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PMID:Proto-RET is rearranged in the new human papillary thyroid cancer cell line PTC-1113A. 868 3

The ret/PTC oncogene is unique to papillary thyroid cancer. Three forms of this oncogene, formed by translocation of three different genes to the tyrosine kinase domain of the ret protooncogene, result in constitutive kinase activation. Correlation with clinical outcome is controversial; ret/PTC-1 has been suggested to predict aggressive behavior. There is no morphological description of ret/PTC-positive tumors. We analyzed 60 thyroid carcinomas for ret/PTC expression to determine correlation with clinical history, disease stage, or tumor morphology. Ribonucleic acid extracted from frozen tissue was reverse transcribed; PCR was performed to amplify ret/PTC-1, 2, and -3. The TPC-1 cell line was the positive control for ret/PTC-1. All tumors were characterized morphologically. Clinical data were collected. The 57 papillary and 3 follicular carcinomas were resected from 44 female patients and 15 males. The average age at diagnosis was 46.2 yr (range. 24-83 yr). Three patients had a history of neck irradiation. At diagnosis, 11 patients had extrathyroidal tumor extension, 20 had lymph node metastases, and 1 had lung metastasis. Thirteen patients had tall cell papillary carcinomas; 3 tumors had focal insular or anaplastic dedifferentiation. The average follow-up was 13.4 months, during which 4 patients had recurrent disease. No deaths occurred. One papillary carcinoma (1.7%) was positive for ret/PTC-1, none was positive for ret/PTC-2, and 2(3.4%) were positive for ret/PTC-3. Although all 3 patients who had tumors containing ret/PTC rearrangements were under the age of 45 yr (range, 26-44 yr) and had small tumors (< 1.2 cm), 2 of these 3 patients presented with lymph node metastases, and the third had lymphatic invasion. ret/PTC oncogene expression did not correlate with radiation history. In summary, ret/PTC oncogene rearrangements were found in 3 of 60 (5%) thyroid carcinomas and were not present in tumors with aggressive morphological features. However, we found ret/PTC rearrangements in young patients (< 45 yr of age) with small thyroid carcinomas showing a predisposition for lymphatic involvement, suggesting a possible role in the development of this subgroup of tumors.
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PMID:ret/PTC-1, -2, and -3 oncogene rearrangements in human thyroid carcinomas: implications for metastatic potential? 914 69

Lymph node metastases at presentation are common in PTC and MTC (about one third of patients at presentation), but are rare in other types of thyroid malignancy, though HCC frequently recurs in lymph nodes. Nodal metastases can be detected by a variety of means, but high resolution ultrasonography may be the method of choice. Unlike other epithelial malignancies, in thyroid cancer neither prognostic significance nor optimal treatment of nodal metastasis are known with certainty. For PTC lymph node metastases at presentation do not seem to adversely affect survival, but do increase the risk of locoregional tumor recurrence. By contrast, in FTC nodal metastases at presentation may adversely affect cause-specific mortality, but because of their rarity definite conclusions are impossible. Except for the oxyphilic variant of FTC (HCC) nodal recurrence in FTC is rare. The most firm evidence of prognostic relevance for nodal metastases in thyroid malignancies exists in medullary thyroid cancer, where most studies suggest that survival and recurrence are both adversely affected by node-positive status at presentation. Primary treatment of nodal metastases is removal of macroscopically affected nodes at initial surgery, optionally supplemented with adjuvant radioiodine treatment in an attempt to reduce recurrence risk. The value, however, of postoperative radioiodine in preventing either nodal recurrence or cancer death in patients with papillary and follicular thyroid cancer remains controversial. Extensive lymph node dissection at presentation offers no advantage (and may cause increased morbidity) in papillary carcinoma, but may be useful in medullary thyroid carcinoma, where nodal metastases seem to increase the risk of cause-specific mortality. In all tumor types postoperative nodal recurrences should primarily be treated surgically.
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PMID:Thyroid cancer nodal metastases: biologic significance and therapeutic considerations. 878 93

We describe a method for screening for dispersed point mutations, based on the observation that RNase frequently cleaves both strands of base pair mismatches in duplex RNA targets. The mismatched substrates are generated by in vitro transcription of wild-type and mutant templates amplified by the PCR or reverse transcription (RT)-PCR; bacteriophage promoters are incorporated into the PCR primers to permit both strands of the products to be transcribed into RNA. Complementary wild-type and mutant transcripts are hybridized and treated with RNase, and the cleavage products are separated on agarose gels and detected by visualization of the ethidium-stained sample under UV light. The method is thus non-isotopic, and since the cleavage products remain double-stranded during analysis, the labor-intensive RNase inactivation steps required in the original procedure can be eliminated. Also, nonspecific background cleavage is reduced so that longer target regions (1 kb) can be screened in a single step. The Non-Isotopic RNase Cleavage Assay (NIRCA) achieved a detection rate of 88%-90% in blind studies in a Factor IX model system, and it was also used to detect unknown p53 mutations in breast tumor samples. NIRCA provides a rapid method for sensitive, non-isotopic, high-throughput genetic screening.
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PMID:NIRCA: a rapid robust method for screening for unknown point mutations. 881 44

This article discusses several unusual forms of primary thyroid neoplasms. The TCV of PTC and insular thyroid carcinoma appears to have a more aggressive clinical behavior than DTC in most patient groups and may respond to thyroid hormone suppression and radioiodine. Anaplastic thyroid carcinoma, which may develop from differentiated thyroid tumors, has a poor prognosis which may be altered by surgery and radiation therapy but not typically by radioiodine and thyroid hormone suppression. Primary squamous cell carcinoma of the thyroid is an unusual entity that may be associated with a clinical syndrome that includes leukocytosis, fever, and hypercalcemia. Primary thyroid lymphoma is frequently associated with Hashimoto's thyroiditis and should be considered especially in older patients with rapidly enlarging thyroid masses. Although there are no studies assessing this issue, it seems reasonable that patients who have undergone thyroidectomy for neoplasms of thyroid cells that are poorly differentiated and do not concentrate radioiodine (e.g., squamous cell, anaplastic) should receive sufficient thyroid hormone suppression, if tolerated, to reduce TSH (third-generation assay) to approximately 0.1 to 0.3 mu U/mL, because TSH may be a growth factor. If, however, the tumor concentrates or responds to radioiodine, suggesting more differentiated cells (e.g., TCV, insular carcinoma), the target TSH level (third-generation assay) should range from 0.01 to 0.1 mu U/mL, as tolerated. Patients with primary thyroid neoplasms arising from cells other than thyrocytes (e.g., lymphoma) can be maintained at a TSH level of 0.5 to 1.5 mu U/mL. Our conclusions and analyses are often based upon small, retrospective, poorly controlled reports, and further studies are required to allow a better understanding of the evaluation and treatment of these neoplasms.
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PMID:Unusual types of thyroid neoplasms. 890 80

Thyroid carcinomas, even when well differentiated, usually appear as hypofunctioning at scintigraphy. We report a case of an aggressive insular thyroid carcinoma presenting as an autonomously functioning thyroid nodule and causing severe thyrotoxicosis. The tumor was metastatic to a cervical lymph node and both lungs. An activating mutation of the TSH receptor gene in both the primary tumor and the lymph node metastasis was found, due to a base substitution at codon 633 (normal guanine at position 1896 replaced by cytosine CAC for GAC causing aspartic acid substitution by histidine). Other known oncogenes (gsp, ras, PTC/ret, trk, met, and p53) were not involved. This is the first description of an activating TSH receptor mutation in a thyroid hyperfunctioning carcinoma in which an aggressive malignant phenotype coexisted with activation of the cAMP cascade and differentiated thyroid functions.
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PMID:Detection of an activating mutation of the thyrotropin receptor in a case of an autonomously hyperfunctioning thyroid insular carcinoma. 936 May 62

Nevoid basal cell carcinoma syndrome (NBCC; Gorlin syndrome), an autosomal dominant disorder linked to 9q22.3-q31, and caused by mutations in PTC, the human homologue of the Drosophila patched gene, comprises multiple basal cell carcinomas, keratocysts of the jaw, palmar/plantar pits, spine and rib anomalies and calcification of the falx cerebri. We reviewed the findings on 105 affected individuals examined at the NIH since 1985. The data included 48 males and 57 females ranging in age from 4 months to 87 years. Eighty percent of whites (71/90) and 38% (5/13) of African-Americans had at least one basal cell carcinoma (BCC), with the first tumor occurring at a mean age of 23 (median 20) years and 21 (median 20) years, respectively. Excluding individuals exposed to radiation therapy, the number of BCCs ranged from 1 to > 1,000 (median 8) and 1 to 3 (median 2), respectively, in the 2 groups. Jaw cysts occurred in 78/105 (74%) with the first tumor occurring in 80% by the age of 20 years. The number of total jaw cysts ranged from 1 to 28 (median 3). Palmar pits and plantar pits were seen in 87%. Ovarian fibromas were diagnosed by ultrasound in 9/52 (17%) at a mean age of 30 years. Medulloblastoma occurred in 4 patients at a mean age of 2.3 years. Three patients had cleft lip or palate. Physical findings include "coarse face" in 54%, relative macrocephaly in 50%, hypertelorism in 42%, frontal bossing in 27%, pectus deformity in 13%, and Sprengel deformity in 11%. Important radiological signs included calcification of the falx cerebri in 65%, of the tentorium cerebelli in 20%, bridged sella in 68%, bifid ribs in 26%, hemivertebrae in 15%, fusion of the vertebral bodies in 10%, and flame shaped lucencies of the phalanges, metacarpal, and carpal bones of the hands in 30%. Several traits previously considered components of the syndrome (including short fourth metacarpal, scoliosis, cervical ribs and spina bifida occulta) were not found to be significantly increased in the affected individuals. This study delineates the frequency of the clinical and radiological anomalies in NBCC in a large population of US patients and discusses guidelines for diagnosis and management.
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PMID:Clinical manifestations in 105 persons with nevoid basal cell carcinoma syndrome. 909 61


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