Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Recurrent variant”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 577 records · Page 32Linked to original sources

Possibility of slow-growing variants in pancreatic adenocarcinoma.

Four patients with advanced pancreatic adenocarcinoma suggesting slow-growing tumors are reported on. Tumors in 2 of the 4 were far-advanced, but both survived for over 3 years after treatment. One demonstrated 165 days of serum CA 19-9 level doubling time (T2CA 19-9), while the other demonstrated 135 days of DUPAN II level doubling time. Late tumor recurrence was observed in the remaining 2 patients who survived over 8 years after surgery, demonstrating long-term T2CA 19-9. A long-term T2CA 19-9 of 141 days was correlated with slow tumor growth in computed tomography (CT) scans in 1 patient, who survived 2.5 years after evidence of recurrent tumor without supplementary therapy. These observations, which suggest slow-growing variants, have not been reported in the literature on pancreatic adenocarcinoma. A significant difference was also seen in tumor-marker doubling time among 6 patients who survived over 3 years and 26 patients who did not (p = 0.02). Thus, the doubling time may characterize certain tumors biologically in a way that is useful in practice for predicting disease outcome.

Adenocarcinoma, Papillary↗

Folate metabolism polymorphisms influence risk of colorectal adenoma recurrence.

Folate intake is inversely related to risk of developing colorectal neoplasia. Associations between risk of colorectal neoplasia and polymorphisms in genes coding for enzymes involved in folate metabolism have also been reported, suggesting a relationship between genotype and development of colorectal neoplasia. To further investigate the effects of folate metabolism genotypes on colorectal neoplasia, we genotyped 546 patients participating in a randomized controlled trial of folate supplementation for the prevention of colorectal adenoma recurrence. A significantly reduced risk of recurrence was observed in patients heterozygous for the MTRR A66G polymorphism [relative risk (RR), 0.64; 95% confidence interval (95% CI), 0.46-0.90] or heterozygous for the MTHFR A1298C polymorphism (RR, 0.71; 95% CI, 0.52-0.97). Furthermore, a significant reduction in recurrence risk was seen in MTRR A66G heterozygotes who received folate supplements but not in those who did not receive folate. Patients heterozygous for the MTHFR C677T polymorphism had a nonsignificant risk reduction (RR, 0.92; 95% CI, 0.69-1.23), as did patients with one or two variant alleles for the MTR A2756G polymorphism (RR, 0.82; 95% CI, 0.60-1.12). No influence on recurrence risk was observed for the TSER, TSER 3R G>C, and TS 1494del6 variants. These findings provide additional support for the hypothesis that germ line variants in folate metabolism genes influence the development of colorectal adenomas.

Adenoma↗

Multiple infiltrating glomus tumors in children.

Two children with multiple infiltrating glomus tumors of the lower extremities presented in infancy with clinical and, in one, radiological, signs of varicose veins. Surgical therapy was followed by multiple recurrences, a phenomenon attributable to the infiltrative properties of the tumor. This variant of multiple glomus tumor may be congenital and is probably hamartomatous in nature.

Adolescent↗

Desmoplastic malignant melanoma: a report on two additional cases.

Two cases of desmoplastic malignant melanoma are described, bringing the total reported to nine. The first developed in a lentigo maligna melanoma and contains the seed of its local recurrence in the primary lesion. The second developed in a clinically apparent congenital nevus and unites the histologic features of the desmoplastic variant with the epithelioid and spindle cell histology of its primary, side by side in a local recurrence. Both primaries were clinically recognized pigmented lesions while the desmoplastic recurrences were amelanotic. Other clinico-pathologic characteristics of DMM as previously described, are confirmed. Light microscopic evidence is presented supporting the view that the desmoplastic reaction is a rare manifestation elicited by a highly invasive spindle cell component of malignant melanoma.

Ankle↗

Effect of calcium antagonists in variant or Prinzmetal angina.

Variant angina, first described by Prinzmetal in 1959, is a syndrome of recurrent ischemic-type chest pain that occurs at rest and is associated with ST segment elevation. The syndrome has been convincingly demonstrated to be caused by temporary occlusion at a site of local spasm. The objectives of this article are to review treatment of the patient with variant angina and to address the important role of calcium antagonists.

Angina Pectoris, Variant↗

Genetic background of Richter transformation of atypical chronic lymphocytic leukemia to diffuse large B-cell lymphoma - a case study.

Atypical chronic lymphocytic leukemia (aCLL) is an indolent lymphoproliferative neoplasm derived from CD19-positive and CD5 or CD23-negative B cells. This paper presents the results of whole genome sequencing (WGS) of lymphoma cells collected from a 29-year-old woman initially diagnosed with aCLL and successfully treated with fludarabine, cyclophosphamide, and rituximab. Eight years later, due to disease progression, she was treated with ibrutinib. After 5 months, her status suddenly deteriorated. PET-CT results suggested Richter transformation (RT). Histopathological examination of nodal lesions confirmed the diagnosis of Diffuse Large B Cell Lymphoma (DLBCL). Finally, the patient was successfully treated with DHAP-R and alloHSCT. WGS of lymphoma cells revealed the presence of pathogenic (COL11A1, MGME1) and likely pathogenic variants (ZMYM3, ALG6, UBA5, and ATG7). Out of these genes, only ZMYM3 is recurrently mutated in B-cell chronic lymphocytic leukemia (B-CLL). The presence of the other lesions requires further studies and indicates the complex molecular background of aCLL transformation to DLBCL. Therefore, the whole-genome variant assessment is worth considering for introduction into a routine procedure at the time of B-CLL diagnosis, especially when RT is suspected.

Humans↗

Rare missense variants in ATP1A2 in families with clustering of common forms of migraine.

Migraine is a recurrent neurovascular disease. Its two most common forms-migraine without aura (MO) and migraine with aura (MA)-both show familial clustering and a complex pattern of inheritance. Familial hemiplegic migraine (FHM) is a rare monogenic subform caused by mutations in the calcium channel gene CACNA1A or the Na(+)/K(+)-ATPase gene ATP1A2. An involvement of FHM genes in the pathogenesis of common forms of migraine is not proven. We therefore systematically screened ATP1A2 in families with several members affected by MA and/or MO. We identified two novel missense alterations [c.520G>A (p.E174 K) and c.1544G>A (p.C515Y)] in two out of 45 families, which were not found in 520 control chromosomes. Functional studies of these variants in Xenopus oocytes by two-electrode voltage clamp measurements and radiochemical determination of ATPase activity showed that C515Y leads to a complete loss of function comparable with the effect of FHM-mutations whereas for E174 K no functional alteration could be found in the in vitro assays. In conclusion we propose that rare variants in ATP1A2 are involved in the susceptibility to common forms of migraine, because of 1) the absence of alterations in controls, 2) the particular pattern of segregation in both families, 3) the high conservation of mutated residues in Na(+)/K(+)-ATPases, 4) the functional effect of C515Y, and 5) the involvement of ATP1A2 in a monogenic form of migraine.

Adult↗

Lack of association of TNFalpha gene polymorphisms and recurrent pregnancy loss in Caucasian women.

The tumor necrosis factor alpha (TNFalpha) gene plays an important role in immunology and inflammation. Variant alleles of TNFalpha are associated with altered RNA and serum protein levels in humans. Conflicting results have been obtained regarding the role of TNFalpha during pregnancy and recurrent pregnancy loss (RPL). This study investigated the relationship between RPL and two polymorphisms in the promoter of the TNFalpha gene (TNFalpha -308 and -863). Genotyping was performed in 168 RPL women and 212 ethnically matched healthy individuals. In addition, we performed analysis of TNFalpha serum protein levels. We demonstrate that neither the polymorphism -308 nor the polymorphism -863 of the TNFalpha gene is associated with RPL in Caucasian women. In addition, we did not find any association between TNFalpha serum levels and the occurrence of RPL in a subset of 36 RPL women and 36 healthy individuals. We conclude that TNFalpha polymorphisms and resting blood TNFalpha levels do not correlate with the propensity to recurrent pregnancy loss in Caucasian women.

Abortion, Habitual↗

Linear basal cell carcinomas: report of multiple sequential tumors localized to a radiotherapy port and review of the literature.

Linear basal cell carcinoma, an uncommon variant of basal cell carcinoma, was first described in 1985. The cases of eight additional patients with this morphologically distinctive variant have been published subsequently. We describe a woman who sequentially developed three linear basal cell carcinomas located within her radiotherapy port. Including our patient, 12 linear basal cell carcinomas have been reported in 10 patients (4 men and 6 women) ranging from ages 40 to 77 years. The tumors were located most often on the head and neck (9 cancers); other sites involved the shoulders (2 cancers) and posterior thorax (1 cancer). All of the tumors were excised without recurrence. Various mechanisms have been postulated to account for this morphologic variant of basal cell carcinomas including a Koebner phenomenon or limited lateral spread of the cancer secondary to dermal fibrosis, or both.

Basal Cell Carcinoma↗

Successful treatment for recurrent painful Hashimoto's thyroiditis by total thyroidectomy.

Painful Hashimoto's thyroiditis is an atypical variant of Hashimoto's thyroiditis characterized by thyroid pain and fever. In patients with this condition, anti-inflammatory agents are not always effective as in those with subacute thyroiditis. Therefore, long-term pain management is an important issue. We report herein four cases of painful Hashimoto's thyroiditis requiring total thyroidectomy to relieve thyroid pain and histologic findings of the thyroid gland. All patients had high titers of anti-thyroperoxidase (TPO) and thyroglobulin antibodies. Three were hypothyroid, and the other was euthyroid. During the first visit, four patients had fever and/or thyroid pain with elevated C-reactive protein or erythrocyte sedimentation rate, and they were treated with oral corticosteroids given continuously or intermittently for 9 to 48 months. Because a reduction or discontinuation of corticosteroids caused recurrent painful attacks, the decision was made to perform surgery. After total thyroidectomy, their symptoms disappeared. The histopathologic characteristics of these hypothyroid cases were advanced fibrosis and destructive thyroid architecture. One euthyroid case showed a mild fibrous change and the presence of foreign body type giant cells. In conclusion, total thyroidectomy is the effective and reliable treatment for patients with recurrent painful Hashimoto's thyroiditis. Pathologic characteristics include advanced fibrosis and destructive thyroid architecture.

Adult↗

Surveillance for recurrent endometrial carcinoma: development of a follow-up scheme.

We examined the method of diagnosis for a group of women who developed recurrent endometrial carcinoma after being rendered clinically disease-free by primary therapy. We then used this information to develop a follow-up protocol that maximizes the chances for detecting recurrence while minimizing surveillance costs. In brief, we evaluated all women with clinical stage I endometrial carcinoma who were treated with curative intent during a 7-year period. Medical records were examined to identify patients who had tumor recurrence diagnosed during follow-up in our clinic. Clinical presentation, time to diagnosis, method of diagnosis, and subsequent outcome were analyzed. This information was used to design a surveillance protocol for further clinical testing. Ninety-six percent of 412 women treated between 1985 and 1992 were clinically disease-free after primary surgery with or without adjuvant treatment. Median follow-up is 64 months. Overall, 44 patients (11%) developed recurrent cancer after a median interval of 14.8 months. Complete follow-up data were available for the 39 patients who had their recurrence diagnosed in our clinic. The cumulative percentages of diagnosed recurrences were 51, 82, and 95% at 12, 24, and 36 months, respectively. Sixteen women (41%) had symptoms that led to the identification of recurrent disease. Recurrences in the 23 asymptomatic women (59%) were diagnosed by physical examination in 13, chest radiograph in 1, serum CA-125 level in 6, vaginal cytology in 1, and computed tomography in 2. Only 1 patient with a grade 1 adenocarcinoma had treatment failure. At the time of analysis, 30 patients with recurrent cancer had died of disease, 6 were alive with disease, and 3 were free of disease. A surveillance scheme consisting of an examination, vaginal cytology, and serum CA-125, combined with immediate evaluation of symptomatic women, could be expected to identify 95% of recurrences. Such an approach, performed at 6- to 12-month intervals for 3 years, could be limited to patients with grade 2-3 adenocarcinomas or variant cell types. However, given the high failure rate of salvage therapy, the prompt detection of recurrence may not convey a survival advantage.

Endometrial Neoplasms↗

[Preliminary results of a multicenter randomized study on the treatment of acute promyelocytic leukemias].

AIM: To study efficacy of maintenance therapy of patients with acute promyelocytic leukemia (APL) in the APL treatment Russian multicenter trial. MATERIAL AND METHODS: The trial was made with participation of 18 hematological departments of clinics in Russia. A total of 68 APL patients entered the trial. The maintenance therapy consisted of 5-day courses of cytostatic drugs which alternated or did not alternate with 5-day courses of ATRA. Cytogenetic tests were made in 31 patients, t(15;17) was detected in 26 of them. Molecular examination conducted in 28 patients discovered chimeric transcript PML/RARa in 26 of them. Of 20 patients examined in Hematological Research Center, 7 (35%) had a bcr 1/2 variant of the transcript PML/RARa, 13 (65%)--bcr 3 variant. RESULTS: 65 patients were eligible for assessment. A complete remission was achieved in 90% cases. No resistance was observed. In follow-up within 30 months the recurrence rate was similar on both treatments. The results of the induction therapy and survival in patients with different variants of the transcripts were also similar. Overall 2.5 year survival for all the patients was 77%, recurrence-free--80%. The survival analysis in patients with leukocytosis higher and lower 10 x 10(9)/l found no statistical differences by the survival. Patients with hyperleukocytosis had higher early lethality than patients with leukocytes under 10 x 10(9)/l (25% vs 5.3%, p = 0.03). CONCLUSION: The APL 06.01 protocol showed high efficacy of the relevant maintenance which provides a complete molecular remission in the majority of patients with probable recurrence-free 2.5 year survival 80%.

Adolescent↗

Increased expression of the metastasis-associated gene Ehm2 in prostate cancer.

BACKGROUND: Alterations of fibroblast growth factors and their receptors contribute to prostate cancer progression by enhancing cell survival, motility, and proliferation. The expression of the FGFR-4 Arg(388) variant is correlated with the occurrence of pelvic lymph node metastasis and biochemical (PSA) recurrence in men undergoing radical prostatectomy. Ehm2 is an androgen-regulated gene that has been associated with metastasis in other systems, so we sought to determine if it is expressed in prostate cancer and if the FGFR-4 Arg(388) variant can increase its expression. METHODS: Expression of Ehm2 was examined by quantitative RT-PCR and Western blotting in prostate cell lines and by quantitative RT-PCR, in situ hybridization, and immunohistochemistry in prostate tissues. The effect of Ehm2 expression on collagen IV adhesion was tested by transient overexpression and RNA interference. RESULTS: Ehm2 expression is upregulated in prostate cancer cell lines and prostate cancer tissues. Expression of the FGFR-4 Arg(388) variant results in increased expression of Ehm2. Increased expression of Ehm2 leads to decreased adhesion to collagen IV, which has been associated with metastasis in cancers. Analysis of tissue microarrays revealed that increased Ehm2 expression is associated with biochemical recurrence after radical prostatectomy, which is indicative of more aggressive disease. CONCLUSIONS: Ehm2 is overexpressed in prostate cancer and may enhance disease progression and metastasis.

Adenocarcinoma↗

Antigenic variation of neutralization-sensitive epitopes of caprine arthritis-encephalitis lentivirus during persistent arthritis.

Caprine arthritis-encephalitis virus (CAEV), a naturally occurring lentivirus of goats, causes disease characterized by virus persistence and recurrent arthritis. These studies demonstrate in vitro neutralization of CAEV infectivity by serum from goats infected with CAEV. Serum neutralizing activity was not detectable until 10 to 36 months postinfection, and titers were relatively low (less than or equal to 1:8). Serum neutralization was caused by antibody and was virus specific. Antigenic variants of CAEV were isolated from cell-free joint fluid of arthritic goats 9 to 18 months postinfection. The delayed appearance of neutralizing antibody and the subsequent development of antigenic variants may promote CAEV persistence in vivo and provide a stimulus for recurrent arthritis.

Animals↗

Gemcitabine, dexamethasone, and cisplatin in patients with recurrent or refractory aggressive histology B-cell non-Hodgkin lymphoma: a Phase II study by the National Cancer Institute of Canada Clinical Trials Group (NCIC-CTG).

BACKGROUND: Gemcitabine has been shown to have activity as a single agent in lymphoma and, when combined with cisplatin, is effective therapy for a number of solid tumors. The authors wished to determine the response rate and toxicity of gemcitabine, dexamethasone, and cisplatin for recurrent or refractory non-Hodgkin lymphoma (NHL). METHODS: Patients with recurrent or refractory diffuse large B-cell NHL or variants (REAL classification), measurable disease, and one previous chemotherapy regimen were eligible. Treatment consisted of gemcitabine 1000 mg/m(2) intravenously (i.v.) on Days 1 and 8, dexamethasone 40 mg orally on Days 1-4, and cisplatin 75 mg/m(2) i.v. on Day 1 (GDP), every 21 days as an outpatient. The primary end point was a response after two cycles. Patients could then proceed to stem cell transplantation (SCT) or receive up to six treatment cycles. RESULTS: Fifty-one eligible patients were evaluable for toxicity and response. The median age of the patients was 57 years (range, 18-84 years) and most had diffuse large-cell lymphoma. After 2 cycles, there were 8 complete responses (CR; 16%) and 17 partial responses (PR; 33%). There was an overall response rate (RR) of 49% (95% confidence interval = 37-63%). The RR afer completion of all protocol chemotherapy (including those who received > 2 cycles of GDP) was 53% (11 CR, 16 PR). Grade 3 and 4 neutropenia occurred in 33% and 39% of patients, respectively. Grade 3 and 4 thrombocytopenia occurred in 24% and 4% of patients, respectively. Seven patients (14%) experienced febrile neutropenia. Of the 35 patients < 66 years, 22 (63%) proceeded to SCT. CONCLUSIONS: GDP is an active regimen in B-cell NHL and can be administered with acceptable toxicity to outpatients. A Phase III trial comparing GDP with standard cisplatin-based chemotherapy is now ongoing through the National Cancer Institute of Canada Clinical Trials Group.

Administration, Oral↗

The gaslight phenomenon--an institutional variant.

A case of paranoid psychosis in an elderly female is reported in which recurrent episodes were apparently induced by the staff of the institution where the patient was a resident. The issues raised by this case are discussed.

Aged↗

TEL gene is involved in myelodysplastic syndromes with either the typical t(5;12)(q33;p13) translocation or its variant t(10;12)(q24;p13).

A t(5;12)(q33;p13) translocation is a recurrent chromosome abnormality in a subgroup of myeloid malignancies with features of both myeloproliferative disorders and myelodysplastic syndromes (MDSs). The molecular consequence of a t(5;12) is a fusion between the platelet-derived growth factor receptor-B gene on chromosome 5 and a novel ETS-like gene, TEL, on chromosome 12. We report on three patients with a t(5;12)(q33;p13) diagnosed as chronic myelomonocytic leukemia, and one case of a t(10;12)(q24;p13) in a progressive MDS, with eosinophilia and monocytosis. Involvement of the TEL gene in these chromosome translocations was investigated by fluorescence in situ hybridization (FISH) with cosmid probes containing selectively the 5' end or 3' end of TEL. Hybridization of these cosmids to the der(5)/der(10) or a der(12), respectively, demonstrated a rearrangement of TEL in both translocations, showing that the t(10;12) is a variant translocation of the t(5;12). Cloning of the fusion cDNA of one case of t(5;12) showed that the breakpoint occurred at the RNA level at exactly the same position as reported by Golub et al (Cell 77:307, 1994). In addition, the TEL gene on chromosome 12 could be localized between two probes previously mapped to 12p13, namely PRB1 and D12S178, leading to a better definition of the position of TEL in this chromosome region. Moreover, in the case involving chromosome 10, the breakpoint occurred between cKTN206 and cKTN312/LYT-10 at 10q24. Clinicohematological data in these studies as well as the restriction mapping of chromosomal breakpoints strongly suggest that (1) common features in MDSs involving the TEL gene are monocytosis and eosinophilia, (2) chromosomes other than no. 5 may be involved and at least a t(10;12)(q24;p13) variant chromosome translocation does exist in these MDSs, and (3) both standard and variant 12p/TEL translocations may be identified by FISH with appropriate probes.

Adult↗

Molecular Characterisation of Treacher Collins Syndrome in a South African Cohort: Novel Disease-Causing Variants in TCOF1 and POLR1D.

BACKGROUND: Treacher Collins syndrome (TCS) is a rare craniofacial disorder characterised by variable expressivity. It is caused by pathogenic variants in the TCOF1, POLR1D, POLR1C, or POLR1B genes. Common clinical features include hypoplasia of the zygomatic complex and mandible, downward-slanting palpebral fissures, lower eyelid anomalies, microtia, and hearing loss. Owing to its phenotypic overlap with other craniofacial syndromes, molecular testing is essential for establishing an accurate diagnosis and guiding effective clinical management. METHODS: Ten South African patients with a suspected clinical diagnosis of TCS underwent targeted next-generation sequencing (NGS) using a custom gene panel including TCOF1, POLR1C, and POLR1D genes. Variants were classified according to ACMG/AMP guidelines, with validation by Sanger sequencing where necessary. RESULTS: Disease-causing variants were identified in six of the ten patients (60%). These included five heterozygous variants in TCOF1 and one homozygous variant in POLR1D. Notably, five of the six variants were identified for the first time in this study. Additionally, a recurrent TCOF1 deletion was identified for the first time in an African family. CONCLUSION: This study expands the mutational spectrum of TCS in general and provides African data in particular. Findings support the use of panel-based NGS for diagnosis in resource-limited settings and highlight the need for population-specific variant data to improve diagnostic accuracy, guide clinical care, and support genetic counselling for affected individuals and their families.

Humans↗