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Background Literature shows that occurrence of comorbidities in people with severe acquired brain injury (sABI) is a common problem in rehabilitation stay. Consequently, patients could require an increase of interventions for diagnosis and treatment of clinical conditions, with a reduction of the rehabilitative take in charge for both clinical and organizational aspects. Aim The first aim was to evaluate the rate of clinical conditions of sABI patients at admission in rehabilitation and the types of rehabilitative interventions performed in the first week; second objective was to explore the impact of clinical conditions on real rehabilitative take in charge. Design Cross sectional study. Setting Inpatient rehabilitation centers. Population The study included data from 586 sABI patients. Methods Collected data regarded anamnestic information, functional status assessed by means of Glasgow Outcome Scale, Levels of cognitive functioning, Early Rehabilitation Barthel Index, comorbidities at admission and type of rehabilitative interventions carried out in first week of rehabilitation stay. Spearman correlation coefficients were applied to detect possible correlations between the number of treatments in first week and clinical variables; through a multiple regression analysis the effect of patient's characteristics on rehabilitative take in charge was explored. Results Data from the sABI patients: mean age 55.1±17.1 years; etiology of sABI was vascular in 315 patients (53.8%), anoxic in 83 (14.2%), neoplastic in 17 (2.9%), infectious in 15 (2.6%), traumatic in 150 (25.6%); 6 subjects (1%) presented a mixed etiology. Need of cardiorespiratory monitoring, pressure sores, infections or presence of multi drug resistant bacteria were the most frequent comorbidities. Passive mobilization, sitting positioning, arousal/awareness stimulation, evaluation and management of dysphagia were the interventions most frequently carried out in the first week. The regression analysis showed that severe neurological and clinical conditions, acute organ failure, cardio-respiratory instability and paroxysmal sympathetic hyperactivity significantly limit access to rehabilitative sessions. Conclusions In sABI patients clinical comorbidities requiring elevated care assistance are frequent at admission in rehabilitation from acute wards and may interfere with rehabilitative take in charge. Clinical rehabilitation impact The knowledge of clinical complexity of sABI patients may improve their care pathways, promoting early and appropriate transition from acute care to rehabilitation settings.

Richter syndrome (RS) represents the transformation of chronic lymphocytic leukaemia (CLL) to aggressive lymphoma. Risk factors of CLL transformation to RS are only partly known. We explored the role of the host genetic background as a risk factor for RS occurrence. Forty-five single nucleotide polimorphisms (SNPs) known to be relevant for CLL prognosis were genotyped in a consecutive cohort of 331 CLL, of which 21 had transformed to RS. After correcting for multiple testing and adjusting for previously reported RS risk factors, the LRP4 rs2306029 TT variant genotype was the sole SNP independently associated with a higher risk of RS transformation (Hazard Ratio: 4·17; P = 0·001; q = 0·047). The enrichment of LRP4 TT genotype in RS was confirmed in an independent series (n = 44) used for validation purposes. The LRP4 protein was expressed in CLL (n =66). Bioinformatic analysis scored LRP4 rs2306029 as a variant with possible deleterious and damaging variant of LRP4. LRP4 genotyping may help the recognition of patients with increased risk of RS at the time of CLL diagnosis.

The integration of molecular and clinical information to tailor treatments remains an important research challenge in chronic lymphocytic leukaemia (CLL). This study aimed to identify genomic lesions associated with a poor outcome and a higher risk of histological transformation. A mono-institutional cohort of 147 cases was used as the test series, and a multi-institutional cohort of 176 cases as a validation series. Genomic profiles were obtained using Affymetrix SNP 6.0. The impact of the recurrent minimal common regions (MCRs) on overall survival was evaluated by univariate analysis followed by multiple-test correction. The independent prognostic significance was assessed by multivariate analysis. Eight MCRs showed a prognostic impact: gains at 2p25.3-p22.3 (MYCN), 2p22.3, 2p16.2-p14 (REL), 8q23.3-q24.3 (MYC), losses at 8p23.1-p21.2, 8p21.2, and of the TP53 locus. Gains at 2p and 8q and TP53 inactivation maintained prognostic significance in multivariate analysis and a hierarchical model confirmed their relevance. Gains at 2p also determined a higher risk of Richter syndrome transformation. The prediction of outcome for CLL patients might be improved by evaluating the presence of gains at 2p and 8q as novel genomic regions besides those included in the 'standard' fluorescence in situ hybridization panel.

A detailed operative procedure of laparoscopic radical hysterectomy (type III) with pelvic and aortic lymphadenectomy after neoadjuvant chemoterapy in treatment of Stage IIb cervical cancer is described.A 50-year-old patient with Stage IIb squamous cell carcinoma of the uterine cervix, who initially was not surgically resectable, received three courses of neoadjuvant chemotherapy that included ifosfamide 5 g/m2, cisplatin 50 mg/m2 and paclitaxel 175 mg/m2 (TIP). Following a partial clinical response to chemotherapy, the patient underwent laparoscopic type III radical hysterectomy with bilateral salpingo-oophorectomy and pelvic and paraaortic lymphadenectomy. The surgical procedure lasted 250 minutes. Blood loss was 310 ml. The patient was discharged on postoperative day 4. The mean length of the resected parametria and paracolpia was 4.1 cm and 2.0 cm, respectively. The number of dissected lymph nodes was 48:29 pelvic and 19 paraaortic nodes. No major intraoperative or postoperative complications occurred. The patient also underwent adjuvant radiation therapy. Follow-up was performed at six months so far.This experience suggests that such a surgical procedure is safe. Laparoscopic radical hysterectomy potentially allows for decreased perioperative morbidity and blood loss, faster recovery and better cosmetic results. Large studies with long term follow-up are needed to confirm that this approach may be proposed as an alternative to conventional surgery.

During pregnancy the asthma has an incidence of 1-4%. In addition to this pathology we find, during pregnancy, an increased incidence of complications both maternal and fetal. These complications, often serious, happen nearly exclusively in patients with severe asthma and/or badly controlled. Therefore, to reduce the risk of beginning of these complications it's necessary to assess correctly the gravity of asthma before becoming pregnant, to make a careful and periodic control of the respiratory function of the patient, to effect a suitable preventive and/or symptomatic pharmacological therapy and to establish specific sanitary-action measures able to prevent the disease becomes acute.

It was observed that fertility and menstrual function in heart-transplanted women, impaired before the operation, become normal with a new heart. The restoration of reproductive function is also confirmed by many cases of pregnancy in heart-transplant recipients, reported in the literature. Twenty-four cases were published worldwide up to 1997, out of which eighteen had a positive result. Also a case personally treated was successful. The outcome of a pregnancy after heart transplantation is, then, generally positive. Nevertheless, such a pregnancy involves important maternal and fetal risks. Thus, the gynecologist has to provide correct information about both such risks and the most suitable contraceptive methods, for these patients. Oral contraceptives are very effective and, in the new low-dose formulations, free from serious adverse effects. No adverse effects have been observed in our patient, who represents the only case, reported in the literature, in which an estroprogestinic contraception was utilized before a pregnancy. In conclusion, during an oral contraception or after a tubal sterilization, pregnancy is really unlikely to occur. Thus, when the couple either has completed the familial nucleus or does not desire offspring, a doubt is at least justified as to whether these safer methods of contraception are advisable in such women.During the period of 1988-97, in the medical literature, 24 cases of pregnancy were reported in women who had undergone heart transplant operations (18 of them with positive outcome). There were 3 cases of spontaneous abortion between the 8th and 14th weeks of pregnancy. The clinical condition of 19 newborns (one case of twins) was good in 15 cases and pathological in 4 cases. The choice of a contraceptive for such women has to take into account the immunosuppressive therapy that is often associated with arterial hypertension. IUDs may increase the risk of infection, but barrier methods are well suited for such women. However, the use of oral contraceptives (OCs) is more controversial because of their effects on lipid and carbohydrate metabolism, on arterial pressure, and coagulation. However, the new types of OCs with less than 35 mcg of ethinyl estradiol do not seem to alter coagulative homeostasis or increase the risk of thromboembolism. Prior to becoming pregnant, among the 24 cases of pregnancy 2 had been dissuaded of using contraception, 2 had used spermicides, 2 others had used barrier methods, and 3 resorted to abortion, while in the rest of the cases the contraceptive was not specified. In one case observed by the authors, the patient had used a low-dose OC for 4 years (0.030 mg ethinyl estradiol and 0.075 mg gestodene) prior to pregnancy and pregnancy occurred when the OC use was suspended at her own decision. No side effects occurred during OC use nor was there any need for increasing the doses of antihypertensive drugs.

The conceptus may be considered as a sort of semi-allogenic graft for the maternal organism, since it shares a half of genomic complement with the father. Nevertheless, its rejection does not take place physiologically during a pregnancy. The mechanisms resulting in the maternal immune tolerance versus the conceptus are not yet completely clarified. Such mechanisms are probably multiple and interacting with each other. In animal and in vitro studies provide evidence suggesting that the following factors are important in producing the maternal immune tolerance: the anatomical position of the fetus; the absence of expression of the class I and II Major Histocompatibility Complex (MHC) molecules in trophoblast tissues; the activity of blocking antibodies; a modification of the immune response; the fetal-placental production of immunosuppressive hormones and substances. Amongst pregnancy-related changes in the immune response, a reduced Natural Killer (NK) cell activity and an increased synthesis of Th2 cytokines (which inhibit the cell-mediated immunity) with an altered Th1/Th2 balance appear to be remarkably important. With regard to fetal-placental hormones, progesterone seems to exert an important immunosuppressive influence mediated by the protein named "Progesterone Induced Blocking Factor" (PIBF). Nevertheless, the real contribution of each of the above mentioned mechanisms still remains to be elucidated in humans.

GnRH-agonist therapy is used in the management of many gynaecological pathologies: uterine fibroids, endometriosis, ovarian cystic pathology, breast cancer, dysfunctional uterine bleeding and, in males, prostatic cancer. In the case of uterine fibroids, this therapy can be used as a pre-treatment before conservative or demolitive surgery or as an alternative to hysterectomy. At the Centre for Therapy of Uterine Pathologies (I Institute of Obstetrics and Gynaecology of the University of Rome "La Sapienza") the use of Gn-RH-A therapy in uterine fibroids has been investigated and results consistent with those of many other groups of study have been obtained. The two most important results are: 1. the decrease of both the myoma's size and the uterine volume; 2. the block of menometrorrhagiae symptoms, with improvement of the haematic crasis and possibility to convert a demolitive surgery to a conservative surgery. GnRH-agonists can represent a definitive treatment for patients with symptomatic uterine fibroids and in perimenopausal age.

The article deals with the medical aspect regarding female genital mutilations (FGM). The cultural origin of this tradition is also considered. Such a practice lies in the partial or complete excision of the external genitalia: it is highly widespread in Central Africa, especially in Ethiopia and Somalia. Currently, approximately 130,000,000 women are involved worldwide. In Italy, it is estimated that about 30,000 women amongst the immigrant population are involved (1). Due to the increasing immigration of women from Countries with FGM tradition, knowledge of the pathologies related to such a practice has become urgently necessary to physicians of western Countries. The aim of this study was to analyze the short-term complications of FGM, which are severe and often even deadly, as well as the long-term ones, which are more likely to be faced in the clinical practice of a western Country physician. In particular, a sample of nine women who had undergone infibulation, amongst the patients admitted at the Departments of Obstetrics and Ginaecology of university of Rome "La Sapienza" during the period 1 January 1985-31 december 1996, has been analyzed. Five out of these women suffered form gynaecological pathologies, whilst four from obstetrical pathologies. Our data on complications associated with FGM are in agreement with those of the world literature and highlight how a more specific expertise is necessary for a correct health care of these women.

This article deals with the current epidemiological features of septic abortion.Forty-two of 431 abortions (9,74%) were diagnosed as septic abortions during 1998 at the I and II Institute of Obstetrics and Gynecology, University of Rome La Sapienza , and are retrospectively analyzed.Thirty-four women (81%) came from an EEC country, whereas 8 (19%) from a developing country. Their mean age was 31,4 years (range: 18-43 years). Eighteen patients (43%) were nulliparous; 24 (57%) multiparous; 14 (33%) had previous abortions, none had previous septic abortions. Among risk factors, premature rupture of membranes was found in 5 cases (12%); whereas amniocentesis, HIV positivity, diabetes, positive urine culture and illegal pregnancy termination procedures were found in 5 further cases. No risk factors were found in 76% of patients.It is observed that, due to medical-scientific advances, previously unknown risk factors have emerged during the last three decades in Western Countries, such as invasive procedures of prenatal diagnosis, IUD contraception and AIDS immunodepression. However, other previously frequent risk factors, such as sepsis from illegal abortion, may emerge again in Countries where abortion is legal (such as Italy), due to massive immigration of clandestine women from developing Countries.

The pineal gland plays an important role in reproductive endocrinology. The epiphysis regulates seasonal variations in reproductive function of seasonally breeding animals. In humans, even if they are not seasonal breeders, the role of the pineal in reproductive endocrinology seems to be important as well. It appears to be of particular importance the endocrine control of the gland on pubertal sexual maturation. Even if not all researchers agree, several data suggest that elevated melatonin levels-characteristic of prepubertal age-keep the hypothalamic-pituitary-gonadal axis in quiescence: thus, an inhibitory effect on pubertal development is exerted. Subsequently, the decreasing serum melatonin with advancing age would result in activation of the hypothalamic pulsatile secretion of GnRH- and therefore of the reproductive axis-with consequent onset of pubertal phenomena. The production rate of melatonin does not change with age and no growth in pineal size from 1 to 15 years of age has been demonstrated by nuclear magnetic resonance (NMR) studies. Therefore the decrease of serum melatonin concentrations has been proposed to be due to the increase in body mass or, according to another hypothesis, to be also temporally linked to sexual maturation. Furthermore, recently, it has been suggested in rats that the pineal influences not only the pubertal sexual maturation, but even the gonadal and genital development and function of offspring, already during intrauterine life. Investigations are needed to evaluate this hypothesis in humans.

Congenital diaphragmatic hernia (CDH) has an incidence of approximately 1:4000 live births. Most frequently the diaphragmatic defect is a left and posterolateral (Bochdalek) one. Prenatal diagnosis is made at ultrasonography; the relevant sonographic features will be described in the paper. Cystic adenomatoid malformation of the lung (CAML), pulmonary sequestration, bronchogenic cysts, pulmonary hypoplasia/agenesia need to be considered in differential diagnosis. In some cases, diagnosis of CDH is not possible "in utero": in such cases, herniation of abdominal viscera into the thorax takes place presumably just at delivery through a small diaphragmatic defect. CDH may be associated with intrauterine growth retardation (IUGR), chromosomal abnormalities (3%) and/or other malformations (10-50%): such as Central Nervous System, digestive, cardiac and urogenital anomalies. Therefore, search of associated malformations and amniocentesis with analysis of fetal karyotype are mandatory, whenever a CDH is diagnosed. CDH is still at present characterised by a high mortality (reportedly, about 45%). Many prognostic factors have been correlated to postnatal outcome of CDH: some of them are valuable prenatally by ultrasonography. However, the role of sonography in the prediction of neonatal outcome is still controversial: in particular, although many ultrasonographic parameters have been proposed, prenatal evaluation of pulmonary hypoplasia (a crucial factor related to postnatal survival) has not proved to be very accurate so far. Nevertheless, it is undisputable that prenatal diagnosis itself represents a crucial prognostic factor for CDH, since it allows birth of the affected fetuses in 3d level Perinatologic Centres provided with a Neonatal Intensive Care Unit and Neonatal Surgery.

Advances in diagnostic techniques and therapy and the institution of both legislative measures and Centres for the protection of mother-infant health are major factors to which the reduced incidence of septic abortion in should probably be ascribed in Western Countries, where it reaches approximately 10%. The aim of this study was to analyse the current problems related to this pathology in a Western Country, such as Italy.Cases of septic abortion observed at the I and II Department of Obstetrics and Gynaecology of University of Rome La Sapienza during 1998 were retrospectively analysed.42 cases of septic abortion were observed. Fever was present in 100 % of cases, genital bleeding in 57 %, abdominal-pelvic pain in 16.7%, genital purulent discharge in one case (2.4%), pain of the fornices at vaginal examination in another (2.4%). Leucocytosis was detected in 21.5% of patients. Disseminated intravascular coagulation (DIC) occurred in one patient (2.4%). No maternal deaths were observed. Antibiotic therapy was carried out in 81% of cases, a uterine curettage in 95.2%.Currently, the possibility of early diagnosis of abortion due to the routine use of ultrasonography and, as a consequence, of early antibiotic therapy, whenever a sepsis is suspected, account for the predominance of mild or even doubtful clinical pictures of this pathology in Western Countries. Nevertheless, severe complications are possible in the case of septic abortion, including septicaemia, septic shock, DIC, renal insufficiency. Thus, a correct and careful attitude of prophylaxis and therapy is required.

Purpose: Few biological prognosticators are useful for prediction of Richter syndrome (RS), representing the transformation of chronic lymphocytic leukemia (CLL) to aggressive lymphoma. Stereotyped B-cell receptors (BCR) may have prognostic effect in CLL progression. We tested the prognostic effect of stereotyped BCR for predicting RS transformation.Experimental Design: The prevalence of stereotyped BCR was compared in RS (n = 69) versus nontransformed CLL (n = 714) by a case-control analysis. Subsequently, the effect of stereotyped BCR at CLL diagnosis on risk of RS transformation was actuarially assessed in a consecutive CLL series (n = 753).Results: RS (n = 69) displayed a higher prevalence of stereotyped BCR (P < 0.001) compared with nontransformed CLL. The actuarial risk of RS transformation was significantly higher in CLL carrying stereotyped BCR (P < 0.001). Among BCR subsets most represented in CLL, subset 8 using IGHV4-39/IGHD6-13/IGHJ5 carried the highest risk of RS transformation [hazard ratio (HR), 24.50; P < 0.001]. Multivariate analysis selected stereotyped BCR (HR, 3.33; P = 0.001) and IGHV4-39 usage (HR, 4.03; P = 0.004) as independent predictors of RS transformation. The combination of IGHV4-39 usage and stereotyped BCR in the same patient identified CLL with a very high risk of RS transformation (5-year risk, 68.7%). The risk carried by stereotyped BCR and IGHV4-39 usage was specific for RS transformation and had no effect on CLL progression without transformation.Conclusions: Analysis of BCR features may help identify CLL patients at risk of RS. A close monitoring and a careful biopsy policy may help early recognition of RS in CLL patients using stereotyped BCR, particularly if combined with IGHV4-39.

Nodal marginal zone lymphoma (NMZL) is a rare, indolent B-cell tumor that is distinguished from splenic marginal zone lymphoma (SMZL) by the different pattern of dissemination. NMZL still lacks distinct markers and remains orphan of specific cancer gene lesions. By combining whole-exome sequencing, targeted sequencing of tumor-related genes, whole-transcriptome sequencing, and high-resolution single nucleotide polymorphism array analysis, we aimed at disclosing the pathways that are molecularly deregulated in NMZL and we compare the molecular profile of NMZL with that of SMZL. These analyses identified a distinctive pattern of nonsilent somatic lesions in NMZL. In 35 NMZL patients, 41 genes were found recurrently affected in ≥3 (9%) cases, including highly prevalent molecular lesions of MLL2 (also known as KMT2D; 34%), PTPRD (20%), NOTCH2 (20%), and KLF2 (17%). Mutations of PTPRD, a receptor-type protein tyrosine phosphatase regulating cell growth, were enriched in NMZL across mature B-cell tumors, functionally caused the loss of the phosphatase activity of PTPRD, and were associated with cell-cycle transcriptional program deregulation and increased proliferation index in NMZL. Although NMZL shared with SMZL a common mutation profile, NMZL harbored PTPRD lesions that were otherwise absent in SMZL. Collectively, these findings provide new insights into the genetics of NMZL, identify PTPRD lesions as a novel marker for this lymphoma across mature B-cell tumors, and support the distinction of NMZL as an independent clinicopathologic entity within the current lymphoma classification.

Richter syndrome (RS) represents the development of diffuse large B-cell lymphoma in the context of chronic lymphocytic leukemia. The scarcity of biologic information about RS has hampered the identification of molecular predictors of RS outcome. We addressed this issue by performing a comprehensive molecular characterization of 86 pathologically proven RS. TP53 disruption (47.1%) and c-MYC abnormalities (26.2%) were the most frequent alterations, whereas common genetic lesions of de novo diffuse large B-cell lymphoma were rare or absent. By multivariate analysis, lack of TP53 disruption (hazard ratio, 0.43; P = .003) translated into significant survival advantage with 57% reduction in risk of death. An algorithm based on TP53 disruption, response to RS treatment, and Eastern Cooperative Oncology Group performance status had 80.9% probability of correctly discriminating RS survival (c-index = .809). RS that were clonally unrelated to the paired chronic lymphocytic leukemia phase were clinically and biologically different from clonally related RS because of significantly longer survival (median, 62.5 months vs 14.2 months; P = .017) and lower prevalence of TP53 disruption (23.1% vs 60.0%; P = .018) and B-cell receptor stereotypy (7.6% vs 50.0%; P = .009). The molecular dissection of RS into biologically distinct categories highlights the genetic heterogeneity of this disorder and provides clinically relevant information for refining the prognostic stratification of patients.

Notch2 mutations represent the most frequent lesion in splenic marginal zone lymphoma., Splenic marginal zone lymphoma (SMZL) is a B cell malignancy of unknown pathogenesis, and thus an orphan of targeted therapies. By integrating whole-exome sequencing and copy-number analysis, we show that the SMZL exome carries at least 30 nonsilent gene alterations. Mutations in NOTCH2, a gene required for marginal-zone (MZ) B cell development, represent the most frequent lesion in SMZL, accounting for ∼20% of cases. All NOTCH2 mutations are predicted to cause impaired degradation of the NOTCH2 protein by eliminating the C-terminal PEST domain, which is required for proteasomal recruitment. Among indolent B cell lymphoproliferative disorders, NOTCH2 mutations are restricted to SMZL, thus representing a potential diagnostic marker for this lymphoma type. In addition to NOTCH2, other modulators or members of the NOTCH pathway are recurrently targeted by genetic lesions in SMZL; these include NOTCH1, SPEN, and DTX1. We also noted mutations in other signaling pathways normally involved in MZ B cell development, suggesting that deregulation of MZ B cell development pathways plays a role in the pathogenesis of ∼60% SMZL. These findings have direct implications for the treatment of SMZL patients, given the availability of drugs that can target NOTCH, NF-κB, and other pathways deregulated in this disease.

We previously showed that cancer cells from papillary, follicular, and anaplastic thyroid carcinomas produce interleukin-4 and interleukin-10, which counteract the cytotoxic activity of conventional chemotherapy through the up-regulation of antiapoptotic molecules. Here, we identify Janus kinase/signal transducers and activators of transcription (STAT) and phosphatidyl inositol 3-kinase (PI3K)/AKT as the down-stream pathways through which these cytokines confer resistance to cell death in thyroid cancer. We found that the absence of suppressors of cytokine signaling (SOCS) molecules allows the propagation of the survival signaling. Exogenous expression of SOCS1, SOCS3, and SOCS5 in the highly aggressive anaplastic thyroid cancer cells reduces or abolishes STAT3 and 6 phosphorylation and PI3K/Akt pathway activation resulting in alteration in the balance of proapoptotic and antiapoptotic molecules and sensitization to chemotherapeutic drugs in vitro. Likewise, exogenous expression of SOCS3 significantly reduces tumor growth and potently enhances the efficacy of chemotherapy in vivo. Our results indicate that SOCS3 regulation of cytokines-prosurvival programs might represent a new strategy to overcome the resistance to chemotherapy-induced cell death of thyroid cancer. We previously showed that cancer cells from papillary, follicular, and anaplastic thyroid carcinomas produce interleukin-4 and interleukin-10, which counteract the cytotoxic activity of conventional chemotherapy through the up-regulation of antiapoptotic molecules. Here, we identify Janus kinase/signal transducers and activators of transcription (STAT) and phosphatidyl inositol 3-kinase (PI3K)/AKT as the down-stream pathways through which these cytokines confer resistance to cell death in thyroid cancer. We found that the absence of suppressors of cytokine signaling (SOCS) molecules allows the propagation of the survival signaling. Exogenous expression of SOCS1, SOCS3, and SOCS5 in the highly aggressive anaplastic thyroid cancer cells reduces or abolishes STAT3 and 6 phosphorylation and PI3K/Akt pathway activation resulting in alteration in the balance of proapoptotic and antiapoptotic molecules and sensitization to chemotherapeutic drugs in vitro. Likewise, exogenous expression of SOCS3 significantly reduces tumor growth and potently enhances the efficacy of chemotherapy in vivo. Our results indicate that SOCS3 regulation of cytokines-prosurvival programs might represent a new strategy to overcome the resistance to chemotherapy-induced cell death of thyroid cancer.

Hairy cell leukaemia (HCL) is a rare B-cell neoplasm for which the molecular mechanisms are largely unknown. High-density genome-wide DNA profiling was performed with Affymetrix 250K arrays to analyse copy number (CN) changes and loss of heterozygosity (LOH) in 16 cases of HCL. Four of 16 cases (25%) demonstrated gross non-recurrent CN deletions. Within the affected regions, we identified genes involved in bone marrow fibrosis (FGF12) and response to treatment (TP53) in individual cases. Large regions (> 5 Mb) of LOH without any concomitant DNA CN changes were identified in 5/16 (31%) HCL and were indicative of uniparental disomy UD. The germline origin of UD was demonstrated in one case for which a matched normal sample was available. Overall analysis of LOH showed that identical loci were recurrently targeted in chromosomes 1, 2 and 6. As a whole, however, HCL showed a remarkably stable genome. This finding adds to several other features that are unique to HCL among mature B-cell tumours.