Impact of constitutional TET2 haploinsufficiency on molecular and clinical phenotype in humans.

Clonal hematopoiesis driven by somatic heterozygous TET2 loss is linked to malignant degeneration via consequent aberrant DNA methylation, and possibly to cardiovascular disease via increased cytokine and chemokine expression as reported in mice. Here, we discover a germline TET2 mutation in a lymphoma family. We observe neither unusual predisposition to atherosclerosis nor abnormal pro-inflammatory cytokine or chemokine expression.

High familial risk in nodular lymphocyte-predominant Hodgkin lymphoma.

Purpose: Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is one of the two established Hodgkin lymphoma (HL) subtypes. The risk factors of NLPHL are largely unknown. In general, genetic factors are known to have a modest effect on the risk of HL; however, familial risk in NLPHL has not been previously examined.

Exome sequencing reveals germline NPAT mutation as a candidate risk factor for Hodgkin lymphoma.

A strong clustering of Hodgkin lymphoma in certain families has been long acknowledged. However, the genetic factors in the background of familial Hodgkin lymphoma are largely unknown. We have studied a family of 4 cousins with a rare subtype of the disease, nodular lymphocyte predominant Hodgkin lymphoma.

Common SNP in pre-miR-146a decreases mature miR expression and predisposes to papillary thyroid carcinoma.

Although papillary thyroid carcinoma (PTC) displays strong heritability, no predisposing germ-line mutations have been found. We show that a common G/C polymorphism (rs2910164) within the pre-miR-146a sequence reduced the amount of pre- and mature miR-146a from the C allele 1.9- and 1.

Platelet-derived growth factor receptor family mutations in gastrointestinal stromal tumours.

Objective: Activating mutations of either KIT or platelet-derived growth factor receptor alpha (PDGFRA) genes are present in the majority of gastrointestinal stromal tumours (GISTs). The type of gene mutation is associated with the aggressiveness of the disease, response to imatinib therapy, and the tumour site in the gastrointestinal tract. However, a subgroup of GISTs does not harbour these mutations.

The role of microRNA genes in papillary thyroid carcinoma.

Apart from alterations in the RET/PTC-RAS-BRAF pathway, comparatively little is known about the genetics of papillary thyroid carcinoma (PTC). We show that numerous microRNAs (miRNAs) are transcriptionally up-regulated in PTC tumors compared with unaffected thyroid tissue. A set of five miRNAs, including the three most up-regulated ones (miR-221, -222, and -146), distinguished unequivocally between PTC and normal thyroid.

MET receptor tyrosine kinase sequence alterations in differentiated thyroid carcinoma.

Activating mutations affecting the MET receptor tyrosine kinase are present in several types of human cancer, particularly in papillary renal cell carcinoma. Papillary thyroid carcinomas commonly express high levels of MET mRNA and protein, suggesting that increased MET signaling may be of importance in the molecular pathogenesis of differentiated thyroid carcinoma. To evaluate the role of MET mutations in thyroid carcinoma, we screened MET exons 2 to 21 for mutations in sporadic papillary, follicular, medullary, and anaplastic thyroid carcinomas using denaturing high-performance chromatography.

KIT and platelet-derived growth factor receptor alpha tyrosine kinase gene mutations and KIT amplifications in human solid tumors.

Purpose: Mutated KIT and platelet-derived growth factor receptor alpha (PDGFRalpha) tyrosine kinases are the principal targets for imatinib mesylate in the treatment of gastrointestinal stromal tumors (GISTs). The frequency of activating KIT and PDGFRA gene mutations in most other histologic types of human cancer is not known.

Materials And Methods: KIT exons 9, 11, 13, and 17 and PDGFRA exons 11 and 17 of 334 human cancers were screened for mutations using sensitive denaturing high-performance liquid chromatography (DHPLC).

Autologous stem cell transplantation in adult patients with peripheral T-cell lymphoma: a nation-wide survey.

Limited experience is available on the feasibility and efficacy of high-dose therapy (HDT) supported by autologous stem cell transplantation (ASCT) in patients with peripheral T-cell lymphoma (PTCL). Therefore, a nation-wide survey was conducted in adult patients transplanted for PTCL in Finland during 1990-2001. After histopathology review, 37 patients were identified.

AMES, MACIS and TNM prognostic classifications in papillary thyroid carcinoma.

The need for total thyroidectomy and extended for lymphadenectomy and the need for postoperative radioiodine ablation in the treatment of papillary thyroid carcinoma is continuously debated. Since less aggressive treatment in low-risk patients has been suggested, several scoring systems have been developed to identify low-risk patients. In the current study, we compared the AMES, MACIS and TNM staging systems in predicting carcinoma-specific mortality in papillary thyroid carcinoma.

Lymphomas diagnosed by percutaneous kidney biopsy.

Background: Occult renal lymphoma clinically mimicking renal medical disease constitutes a diagnostic challenge to nephrologists, radiologists, and renal pathologists. The clinical and radiological findings, mostly nonspecific or inconclusive, seldom obviate the need for a kidney biopsy.

Methods And Results: We report 5 new cases of diffuse bilateral renal lymphoma diagnosed by percutaneous kidney biopsy, all presenting with acute renal failure (ARF) of unknown cause.

Cyclin A and Ki-67 expression as predictors for locoregional recurrence and outcome in laryngeal cancer patients treated with surgery and postoperative radiotherapy.

Purpose: To investigate the association between the cancer cell proliferation fraction and the risk of recurrence in laryngeal cancer patients treated without systemic therapy.

Methods And Materials: Paraffin-embedded tumor samples from 90 laryngeal cancer patients were stained for cyclin A and the Ki-67 antigen by immunohistochemistry. The patients were treated with partial or total laryngectomy followed by postoperative radiotherapy to a total dose of 50 Gy or greater.

Primary treatment with autologous stem cell transplantation in mantle cell lymphoma: outcome related to remission pretransplant.

Objectives: The aim of the first Nordic mantle cell lymphoma (MCL) protocol was to study the clinical significance of an augmented CHOP induction chemotherapy followed by high-dose chemotherapy and autologous stem cell transplantation (ASCT) and to examine the prognostic significance of stem cell contamination rates in newly diagnosed patients with MCL.

Patients And Methods: Forty-one newly diagnosed patients below 66 yr were enrolled and given three series of an augmented CHOP regimen. Responders underwent stem cell mobilization with a fourth course of CHOP, stem cell harvest and ASCT.

Lymphotoxin beta expression is high in chronic lymphocytic leukemia but low in small lymphocytic lymphoma: a quantitative real-time reverse transcriptase polymerase chain reaction analysis.

Background And Objectives: The lymphotoxin beta (LTB) gene, localized to the major histocompatibility complex region on chromosome 6p21.3, has an important role in the formation of germinal center reactions and regulation of immune response and apoptosis. Our aim was to determine LTB gene expression in different hematologic neoplasias.

Abnormal expression of apoptosis-related genes in haematological malignancies: overexpression of MYC is poor prognostic sign in mantle cell lymphoma.

The expression of apoptosis-related genes BCL2, BAX, BCL2L1, BCL2A1, MCL1, DAPK1 and MYC was studied by quantitative real-time polymerase chain reaction on total RNA samples from patients with acute lymphoblastic leukaemia (ALL, n = 16), acute myeloid leukaemia (AML, n = 27), chronic myeloid leukaemia (CML, n = 12), mantle cell lymphoma (MCL, n = 19) and chronic lymphoid leukaemia (CLL, n = 32). BCL2, BAX, BCL2A1, MCL1, DAPK1 and MYC were overexpressed in all patient groups. BCL2L1 was underexpressed in CLL and CML, but not in AML, ALL and MCL.

Predictive factors for blastoid transformation in the common variant of mantle cell lymphoma.

Approximately 20% of the mantle cell lymphoma (MCL) patients present with the blastoid variant at diagnosis. Blastoid changes may occur also during the course of the disease, but factors related to blastoid transformation are poorly understood. In the present study, the incidence and predictive factors for blastoid transformation were analysed among 52 patients who primarily had the common variant of MCL and one or more biopsies taken at the time of disease progression.

Hepatocyte growth factor receptor, matrix metalloproteinase-11, tissue inhibitor of metalloproteinase-1, and fibronectin are up-regulated in papillary thyroid carcinoma: a cDNA and tissue microarray study.

Purpose: To screen and validate the global gene expression in papillary thyroid carcinoma (PTC) using cDNA expression arrays and immunohistochemistry on tumor tissue microarrays in an attempt to find genes that may be of importance in the molecular pathogenesis and malignant progression of PTC.

Experimental Design: Eighteen PTC tissue specimens were compared with three morphologically normal thyroid specimens by applying Atlas Human Cancer 1.2 Array membranes printed with cDNAs of 1176 human genes involved in cancer.

Investigatory and analytical approaches to differential gene expression profiling in mantle cell lymphoma.

Mantle cell lymphoma (MCL) is a non-Hodgkin's lymphoma of B-cell lineage. The blastoid variant of MCL, characterized by high mitotic rate, is clinically more aggressive than common MCL. We used the cDNA array technology to examine the gene expression profiles of both blastoid variant and common MCL.

Ki-67 expression level, histological subtype, and the International Prognostic Index as outcome predictors in mantle cell lymphoma.

Objectives: Mantle cell lymphoma (MCL) is characterised by translocation t(11;14) (q13;q32) leading to rearrangement of bcl1/CCND1 and overexpression of the cell-cycle regulatory protein cyclin D1. We assessed the significance of the cell proliferation rate as an outcome predictor with the five components of the International Prognostic Index (IPI) and the histological subtypes of MCL.

Patients And Methods: The hospital case records and histopathological material of 127 patients diagnosed with MCL in a single centre were reviewed.

Autologous stem cell transplantation in patients with mantle cell lymphoma.

High-dose therapy followed by autologous stem cell transplantation (ASCT) has been considered a potential treatment approach in order to improve the poor prognosis in mantle cell lymphoma (MCL), but its role has not yet been clearly established. We analyzed retrospectively the outcome and prognostic factors in 48 consecutive patients with MCL scheduled for ASCT in five transplant centers. In 14 patients (29%), a sufficient amount of stem cells could not be collected.

Mucoepidermoid carcinoma of the thyroid: a tumour histotype characterised by P-cadherin neoexpression and marked abnormalities of E-cadherin/catenins complex.

The cadherin/catenins complex regulates cell-cell adhesion and motility and is believed to have an invasion suppressor role. Primary mucoepidermoid carcinoma of the thyroid (MECT) is a rare tumour characterised by a distinct morphological appearance and a questionable histogenesis. The coexistence of papillary thyroid carcinoma (PTC) foci in many patients with MECT suggests an association between the two tumour histotypes.

Alterations in the suppressor gene PPP2R1B in parathyroid hyperplasias and adenomas.

Deletion of chromosome 11q23 is a common alteration in parathyroid adenomas and hyperplasias. A new potential suppressor gene PPP2R1B encoding the beta isoform of the A subunit of the serine/threorine protein phosphatase 2A was recently identified and localized to chromosome 11q23. We performed polymerase chain reaction-based single-strand conformation polymorphism and direct sequencing on six parathyroid hyperplasias and 12 adenomas to evaluate the role of PPP2R1B in the pathogenesis of parathyroid lesions.