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Papers by Guy Rosner

Current Colorectal Cancer Reports, 2009

Hereditary nonpolyposis colorectal cancer (HNPCC) accounts for most hereditary colorectal cancers... more Hereditary nonpolyposis colorectal cancer (HNPCC) accounts for most hereditary colorectal cancers. The detection of families with HNPCC enables disease surveillance and clinical management, which significantly reduce morbidity and mortality. Mutations in DNA mismatch repair (MMR) genes underlie HNPCC and cause microsatellite instability (MSI). Although screening for pathogenic mutations in DNA MMR genes is time consuming and costly, MSI-based molecular diagnosis

Familial Cancer, 2015

Bi-allelic MUTYH gene mutations are associated with a clinical phenotype of multiple colorectal a... more Bi-allelic MUTYH gene mutations are associated with a clinical phenotype of multiple colorectal adenomas and an increased risk for colorectal cancer (CRC). It is unclear whether mono-allelic MUTYH gene carriers (heterozygotes) are also at increased risk for even few adenomas or cancer. In order to clarify an association between MUTYH heterozygotes and adenomas, we evaluated the frequency and types of MUTYH mutations and variants in 72 North-African Jews having few (C3) colorectal adenomas with or without early onset (\50 years) CRC compared to 29 healthy controls. Germ-line DNA was analyzed for a panel of 6 MUTYH mutations and variants, and Sanger sequencing of the entire MUTYH gene was performed for mono-allelic MUTYH mutation carriers. APC gene mutations and Lynch syndrome were excluded in the relevant cases according to accepted clinical criteria. Twenty-two of the 72 adenoma subjects (30.5 %) had MUTYH mutations or variants. Nine were homozygotes or compound heterozygotes: all had [10 adenomas and one had CRC. Thirteen others were mono-allelic carriers (heterozygotes) of a single MUTYH mutation: six had more than ten adenomas and seven had less than ten adenomas; of these 13 mono-allelic carriers, six had a neoplasm: three CRCs and three extra-intestinal tumors. Eleven of the thirteen mono-allelic carriers with adenomas had a family history of cancer in first or second degree relatives. A multivariable model showed positive correlation between G396D, Y179C and 1186 ins GG mutations and number of adenomas (OR 8.6, 10.2 and 14.4, respectively). The Q324H variant was negatively associated with the number of adenomatous polyps ). In conclusion, MUTYH mutations are prevalent among Jews of North-African origin with colorectal adenomas with or without early onset CRC. Mono-allelic MUTYH carriers with a family history of cancer had a clinical phenotype that varied from having only few adenomas to multiple ([10) adenomas. These findings support MUTYH testing in patients with even few adenomas and suggest the consideration of increased surveillance in mono-allelic carriers with a family history of cancer.

The Israel Medical Association journal : IMAJ, 2010

Patients with multiple (< 100) colorectal adenomatous polyps are at increased risk for colorec... more Patients with multiple (< 100) colorectal adenomatous polyps are at increased risk for colorectal cancer. Genetic evaluation of those patients who test negative forAPCgene mutation is both a clinical and economic burden but is critical for counseling and surveillance. In Israel, this is confounded by the fact that national health insurance does not fully cover genetic evaluation of APC gene exon 16. To perform a comprehensive genetic evaluation of APC gene mutation-negative polyposis patients with the aim of developing a future evaluation protocol. Genetic analyses were performed in 29 APC gene mutation-negative Jewish individuals with 5 to > or = 40 colonic adenomas who did not fulfill Amsterdam (clinical) criteria for Lynch syndrome. Analyses included completion of APC gene exon 16 sequencing, analysis for APC gene copy number variations (deletions or duplications), MUTYH gene sequencing, and microsatellite instability in CRC patients fulfilling "Bethesda" (laborat...

The Israel Medical Association journal : IMAJ, 2009

Pancreatic cancer is not a common malignancy in Israel, but it is the third most common cause of ... more Pancreatic cancer is not a common malignancy in Israel, but it is the third most common cause of cancer mortality, attributable to a lack of screening tests, inaccessibility of the pancreas, and late cancer stage at diagnosis. We reviewed the epidemiology, known risk factors and screening methods available in Israel and describe the Israeli national consortium that was established to identify persons at risk and decide on screening methods to detect and treat their early-stage pancreatic cancer. In collaboration with the Israel National Cancer Registry, we evaluated the incidence and trends of the disease in the Jewish and non-Jewish populations. The consortium reviewed known lifestyle risk habits, genetic causes, and screening methodologies used and available in Israel. Overall, there are about 600 new patients per year, with the highest incidence occurring in Jewish men of European birth (age-standardized rate 8.11/10(5) for 2003-06). The 5 year survival is about 5%. The consortiu...

Pediatric research, 2006

Annual Review of Genomics and Human Genetics, 2009

In Israel, genetic screening and testing are widespread and are on the rise. The socialized medic... more In Israel, genetic screening and testing are widespread and are on the rise. The socialized medical system, the governmental National Program for the Detection and Prevention of Birth Defects, the central registry of genetic disorders, and the availability of medical genetic units influence the extensive utilization of genetic services. Israeli society is a complex one-ethnically, religiously, and culturally diverse, comprised of Jews of many ethnic backgrounds, as well as Christian and Moslem Arabs, Druze, and Bedouins. Multiple founder mutations have been documented in these various ethnic populations, often down to the level of specific villages or tribes. Although carrier screening and prenatal diagnostic testing are well established in the general population, the rejection of pregnancy termination by many religious communities often prevents participation in testing. Culturally appropriate genetic programs have been initiated in religious Jewish and non-Jewish communities in an attempt to overcome cultural barriers and reduce the frequency of severe genetic diseases nationwide.

$Research paper thumbnail of Bioavailability of 239+240Pu and 137Cs in aerosols and deposited dusts: a comparative study by fractional extraction$

Radiation and Environmental Biophysics, 2004

The bioavailability of (137)Cs and (239+240)Pu in soil, dust and aerosols has been determined by ... more The bioavailability of (137)Cs and (239+240)Pu in soil, dust and aerosols has been determined by applying a fractional extraction procedure. In aerosols, 47-57% of (137)Cs was found to be easily exchangeable. This differs significantly from soil and deposited dust samples collected on a nearby street as well as on grassland where (137)Cs was quantitatively found in the acid-soluble fraction and the residue. A similar difference was observed for (239+240)Pu: 47% of (239+240)Pu in aerosols was associated with the organic fraction, while in soil and deposited dust from grassland 63-75% of (239+240)Pu was found in the acid-soluble fraction. In deposited street dust, 53% of (239+240)Pu was associated with the oxide fraction.

Prenatal Diagnosis, 2007

Objective Isolated nonvisualized fetal gallbladder (INVFGB) is relatively rare. In most cases, th... more Objective Isolated nonvisualized fetal gallbladder (INVFGB) is relatively rare. In most cases, the gallbladder will eventually be detected. In some cases however, INVFGB may be associated with serious abnormalities, cystic fibrosis (CF), aneuploidy, and agenesis of the gall bladder. We describe a clinical evaluation of prenatally diagnosed INVFGB.

Postgraduate Medical Journal, 2006

Background: Since the adoption of a universal hepatitis B immunisation strategy, the reported inc... more Background: Since the adoption of a universal hepatitis B immunisation strategy, the reported incidence of acute hepatitis B has declined dramatically worldwide including in Israel. However, new cases of acute hepatitis B still occur. The aim of this study was to describe the incidence of acute hepatitis B in a referral area, routes of transmission, and outcome. Methods: The charts of all new hepatitis B patients, who visited the clinic in the years 2002 and 2003 (January 2002 to December 2003), were reviewed. The main criteria for a diagnosis of acute hepatitis B were transient increase of alanine transaminase activity, and hepatitis B surface antigen seroconversion.

Pediatric Research, 2006

Abnormalities in DNA copy number are frequently found in patients with multiple anomaly syndromes... more Abnormalities in DNA copy number are frequently found in patients with multiple anomaly syndromes and mental retardation. Array-based comparative genomic hybridization (array-CGH) is a high-resolution, whole-genome technology that improves detection of submicroscopic aberrations underlying these syndromes. Eight patients with mental disability, multiple congenital anomalies, and dysmorphic features were screened for submicroscopic chromosomal imbalances using the GenoSensor Array 300 Chip. Subtelomeric aberrations previously detected by fluorescence in situ hybridization (FISH) analysis were confirmed in two patients, and accurate diagnosis was provided in two previously undiagnosed complex cases. Microdeletions at 15q11.2-q13 in a newborn with hypotonia, cryptorchidism, and hypopigmentation were detected with few discrepancies between the array results and FISH analysis. Contiguous microdeletion of GSCL, HIRA and TBX1 genes at 22q11.2 was identified in a previously undiagnosed boy with an unusual presentation of the VCF/DiGeorge spectrum. In a newborn with aniridia, a borderline false-negative WT1 deletion was observed, most probably because of differences between the size of the genomic deletion and the microarray probe. A false-positive rate of 0.2% was calculated for clone-by-clone analysis, whereas the per patient false-positive rate was 20%. Array-CGH is a powerful tool for the rapid and accurate detection of genetic disorders associated with copy number abnormalities and can significantly improve clinical genetic diagnosis and care.

Liver International, 2006

Liver International, 2004

Background: Experience with lamivudine treatment of immunocompetent patients with acute hepatitis... more Background: Experience with lamivudine treatment of immunocompetent patients with acute hepatitis B is limited. Aim of study: To evaluate the safety and efficacy of lamivudine for the treatment of acute severe hepatitis B virus (HBV) infection in immunocompetent adults. Patients and Methods: Fifteen patients (10 men, 5 women, mean age 34.3 AE 7.3 years) with severe acute HBV infection were treated with lamivudine 100 mg daily for 3-6 months, starting 3-12 weeks after onset of infection. Prior to treatment, 5 patients had grade 1-4 encephalopathy; all patients had severe coagulopathy (mean INR was 4.5 AE 6.4), and all patients had evidence of severe hepatocyte lysis (mean alanine aminotransferase 3738 AE 1659 U/L, and mean total serum bilirubin 18 AE 6.8 mg/dl). All patients had evidence of highly replicative HBV (mean HBV DNA 13.5 Â 10 6 AE 11 Â 10 6 copies/ml). Results: Thirteen patients (86.6%) responded to treatment. Encephalopathy disappeared within 3 days of treatment and coagulopathy improved within 1 week. Serum HBV DNA was undetectable (by polymerase chain reaction) within 4 weeks, and serum liver enzyme levels normalized within 8 weeks. Two patients in whom lamivudine therapy was delayed developed fulminant hepatitis and underwent urgent liver transplantation. (One died of vascular complications 1 month later). The 11 patients who were serum HBeAgpositive before treatment seroconverted, and HBeAb developed within 12 weeks in 9 of them; HBsAg was undetectable in all 11 tested patients, and protective titer of HBsAb developed within 12-16 weeks in 9 of them. Therapy was well tolerated in all cases. Conclusions: These data indicate that lamivudine induces a prompt clinical, biochemical, serological and virological response in immunocompetent patients with de novo HBV infection. Lamivudine may prevent the progression of severe acute disease to fulminant or chronic hepatitis and should be considered for use in selected patients. A large randomized controlled, double-blind prospective study is needed.

International Journal of Cancer, 2007

Israeli Arabs have been at low risk for colorectal cancer (CRC) and had mainly proximal cancer, b... more Israeli Arabs have been at low risk for colorectal cancer (CRC) and had mainly proximal cancer, but increasing CRC is now noted. We examined this trend and CRC site and compared them to the total Jewish population and to the low-risk Jews of Asian-African origin. Israel Cancer Registry CRC data, 1982 Arabs and Jews was computed by gender, age and site: rectal cancer included recto-sigmoid junction; ''right-sided'' CRC included the proximal colon up to and also the splenic flexure. During 1982-2002, Arab CRC trends increased significantly in both sexes due to left-sided CRC (women, p 5 0.01; men, p 5 0.02) and rectal cancers (p 5 0.05). Left-sided CRC increased significantly in both men and women aged 65 years (p 5 0.02). Comparing 1982Comparing -1984Comparing to 2000Comparing -2002, the proportion of right-sided CRC decreased in both genders (p < 0.01) from 39.4 to 27.1% of male CRC, and from 44.8 to 31.3% in females. In general, this pattern of increasing rectal and left-sided CRC had been seen over a decade earlier in Jews of Asian-African origin and then their trend reversed during the last decade. In conclusion, there is a recent trend for leftsided CRC in Israeli Arabs, probably related to their changing life style. These results should influence their cancer preventive lifestyle recommendations, and CRC screening and diagnostic methodologies used. ' 2006 Wiley-Liss, Inc.

Familial Cancer, 2012

Clinical features usually initiate evaluation for Lynch Syndrome (LS) but some colorectal cancer ... more Clinical features usually initiate evaluation for Lynch Syndrome (LS) but some colorectal cancer (CRC) histopathology findings are compatible with high microsatellite instability (MSI-H) that also occurs in LS. This led to the suggestion that pathologists request MSI analysis, which is an expensive addition to routine histology. We aimed to see if a Gastrointestinal Pathologist could identify MSI-H features with reproducibility and high (95%) specificity (MSI-H 95%). Histopathology of all CRCs received during 2005 and 4 MSI-H controls were scored using 2 published methods, &amp;amp;amp;amp;amp;amp;amp;quot;MsScore&amp;amp;amp;amp;amp;amp;amp;quot; and &amp;amp;amp;amp;amp;amp;amp;quot;PathScore&amp;amp;amp;amp;amp;amp;amp;quot;. MSI analysis was performed on CRCs scored by either method as probable MSI-H 95% and results compared. To examine reproducibility of histopathology, 100 coded slides, including 25 scored MSI-H 95% and 75 scored low, were re-examined to now identify those needing MSI analysis. Costs were evaluated for identifying MSI-H with or without scoring. All 227 CRCs were scored for possible MSI-H 95%; 24 had high scores and MSI analysis. DNA analysis proved 14 MSI-H, PathScore identified 13 (95%), MsPath identified 9 (64%), histopathology alone identified 7 (50%). Reproducibility for identifying histopathology characteristics of MSI-H at re-examination, without scoring, was &amp;amp;amp;amp;amp;amp;amp;quot;moderate agreement&amp;amp;amp;amp;amp;amp;amp;quot; (Kappa statistic = 0.4615). Costs for identifying MSI-H by PathScore were the lowest, $436/identification. Conclusions; PathScore identified the most proven MSI-H CRCs at lowest cost and even an experienced gastrointestinal pathologist has difficulties identify MSI-H without scoring. So, scoring can be facilitated by a computerized evaluation form for routine CRC histology, prompting score computation and recommendation for MSI analysis with high specificity.