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Colorectal cancer is the third leading cause of cancer-related death in the United States. About 15% of colorectal cancers are associated with microsatellite instability (MSI) due to loss of function in the DNA mismatch repair pathway. This subgroup of patients has better survival rates and is more sensitive to immunotherapy. However, it remains unclear whether microsatellite stable (MSS) patients with colorectal cancer can be further stratified into subgroups with differential clinical characteristics. In this study, we analyzed The Cancer Genome Atlas data and found that Chr20q amplification is the most frequent copy number alteration that occurs specifically in colon (46%) and rectum (61%) cancer and is mutually exclusive with MSI. Importantly, MSS patients with Chr20q amplification (MSS-A) were associated with better recurrence-free survival compared with MSS patients without Chr20q amplification (MSS-N; P = 0.03). MSS-A tumors were associated with high level of chromosome instability and low immune infiltrations. In addition, MSS-A and MSS-N tumors were associated with somatic mutations in different driver genes, with high frequencies of mutated TP53 in MSS-A and mutated KRAS and BRAF in MSS-N. Our results suggest that MSS-A and MSS-N represent two subtypes of MSS colorectal cancer, and such stratification may be used to improve therapeutic treatment in an individualized manner. Significance: This study shows that chromosome 20q amplification occurs predominately in microsatellite-stable colorectal cancer and defines a distinct subtype with good prognosis, high chromosomal instability, distinct mutation profiles, and low immune infiltrations.

Patient: Female, 36 Final Diagnosis: Small cell sarcoma Symptoms: Mass to right upper thigh Medication: — Clinical Procedure: Surgical resection Specialty: Oncology Objective: Rare disease Background: A subset of undifferentiated small round cell sarcomas (USRCSs) is currently being recognized as emerging entities with unique gene fusions: CIC-DUX4 (the area of focus in this article), BCOR-CCNB3, or CIC-FOXO4 gene fusions. CIC-DUX4 and CIC-FOXO4 fusions have been reported in soft tissue tumors, while BCOR-CCNB3 fusion with an X chromosomal inversion was described in both bone and soft tissue tumors. CIC-DUX4 fusion can either harbor t(4;19)(q35;q13.1) or t(10;19)(q26.3;q13), while t(4;19)(q35;q13.1) is reported more commonly. Case Report: The aim of this study is to share a new case report of a 36-year-old woman who had a rapidly growing mass in her right upper thigh, which was found to be an undifferentiated small round cell sarcoma with t(4;19) (q35;q13.1) CIC-DUX4 fusion was confirmed by cytogenetic testing. Combined modality treatment with surgery, radiation, and chemotherapy was used and achieved a good response. A review of the literature of the reported cases with CIC-DUX4 fusions including both t(4;19) and t(10;19) translocations revealed a total of 44 cases reported. Out of these 44 cases, 33 showed t(4;19)(q35;q13.1) translocation compared to 11 cases with t(10;19)(q26.3;q13). Conclusions: Undifferentiated small round cell sarcomas are aggressive tumors. Their treatment includes surgery, chemo-therapy, and radiation. Resistance to chemotherapy is common. Lung and brain are common sites of metastasis, with associated poor prognosis. Generally, median survival is less than 2 years. Newer techniques have been developed recently which helped identify a subset of previously unclassifiable sarcomas, with promising prognostic value.

A cause of antiepileptic medication resistant seizures presenting in neonates and young infants is pyridoxine-dependent epilepsy (PDE), an organic aciduria, which is due to recessive mutations in the ALDH7A1 gene, resulting in deficiency of antiquitin. Since the discovery of molecular basis of this disorder, a few patients have been reported with a similar clinical phenotype but without evidence of antiqutin dysfunction. We report on a patient who had carried a clinical diagnosis of PDE for 7 years, but who was than shown to have normal ALDH7A1 sequencing and the absence of biomarkers characteristic of this familial epilepsy. Array comparative genomic hybridization (CGH) demonstrated a 1.5-Mb terminal deletion of the long arm of chromosome 20, which included deletion of the KCNQ2 and CHRNA4 genes, both of which have been associated with specific epilepsy syndromes. We suggest that this boy's neonatal epilepsy and neurodevelopmental disabilities are secondary to this deletion and that his clinical response to pyridoxine was coincidental. This patient's history emphasizes the utility of array CGH in the evaluation of children with epilepsy of unknown etiology.

Two patients with Klinefelter's syndrome (KS) and two patients with hypogonadism (HG) have been studied clinically and cytogenetically. Originally three of the patients were clinically diagnosed as HG, but according to cytogenetic findings one of them was found to be a case of KS. Chromosomal differences in these four patients with related syndromes were compared and the theoretical possibility for the origin of structural exchange between the X and Y chromosomes in mitosis as the cause for hypogonadism is discussed.

The pattern of fluorescence of the 24 human chromosome types is described and illustrated by means of one karyotype (Fig. 1) and one idiogram (Fig. 2). The fluorescent bands are of two main types: those with dark shades (dark and dim), called negative, and those with light shades (light, bright and intense), called positive. The number, size and shade of the fluorescent bands are recorded and each band is located in the human idiogram. The locations are determined as distances from the centromere in each chromosome, the unit of distance being 1% of the female haploid chromosome length. A nomenclature is proposed, in which the bands are numbered from the centromere to the chromosome ends. Since the centromeric regions in all human chromosomes show negative fluorescence, it follows that negative bands will have 0 or even numbers and positive bands odd numbers. The survey of the morphological data resulted in the finding of some suggestive trends with possible bearing on karyotypic evolution in man.

Chromosome 9 had additional chromosomal material at the end of the long arm in 15 of 16 patients with Ph1 positive CML. The remaining patient had a normal chromosome 9but additional material on 19. The amount of additional material was approximately the same as that lacking on chromosome 22. Translocations between 9 and 22, and 19 and 22, respectively, are therefore suggested. One patient with Ph1 negative CML had no detectable additional chromosomal material on any chromosome including chromosome 9, which gives further support to the view that there is indeed a translocation in Ph1 positive patients. Extra chromosomes appeared in two of three Ph1 positive patients in the blastic stage. Both patients had extra number 8 chromosomes and double Ph1, and one patient had further extra chromosomes, i.e. 7, 11, 12, 16, 17 and 19.

Marrow cells from an untreated man with preleukaemia were found to have trisomy for the long arm of chromosome 1 which was translocated to the end of the long arm of number 11, i.e., 46, XY, -11, +t (1:11) (q11 or q12; q25). The same abnormality was found in metaphases from 8 individual granulocytic colonies. With development of acute myelomonocytic leukaemia, in addition to the basic chromosome abnormality, trisomy of chromosome 8 and an extra chromosome number 19 with partial deletion were found. Fibroblasts grown from marrow biopsy material showed a normal diploid complement, 46, XY.

A child with partial trisomy of the long arm of chromosome 7 and the short arm of chromosome 20 is described. The aberration was inherited from the mother, who had a complex balanced translocation, t(6; 7; 20).

The C3 complement system was examined in our Danish material of normal families, which had earlier been examined for 59 marker systems, and in a myotonic dystrophy family material. A total of 8 alleles were recognized, with allele frequencies as follows: C3*S = 0.7902, C3*F = 0.2018, C3*S rare (3 lumped together) = 0.0036, C3*F rare (2 lumped together) = 0.0024; a silent allele was recognized in three families and its frequency estimated to C3*QO = 0.002. The distribution of unrelated individuals did not deviate significantly from the Hardy-Weinberg expectation, it was not significantly different between the sexes, and for none of the mating types was there any significant deviation from the expected ratios of children. As to linkage relationships of C3 with marker systems and with myotonic dystrophy, there was evidence (most of it first presented at the 6th International Congress of Human Genetics, Jerusalem 1981) for synteny with ABH secretion (Se): C3-Se (males) z = 4.35, theta = 0.12 and with Lewis secretion (LES): C3-LES (males z = 3.63, theta = 0.04). There were indicative or suggestive lod scores for Se-PEPD (males & females z = 2.41, theta = 0.00), C3-Lu (z = 1.88, theta = 0.15), C3-DM (z = 1.69, theta = 0.06) and PEPD-C3 (male z = 0.95, theta = 0.17). The most likely sequence of these 6 systems would appear to be LES-C3-DM-(Se-PEPD)-Lu and the synteny would reside on chromosome 19.

Dermatoglyphic studies were performed on 24 aborted human embryos in whom major chromosomal aberrations had been revealed by amniocentesis. Prints were obtained from the embryos by the Hollister method. An analysis was done using patterns on finger tips and the atd angle was measured in degrees. The Penrose classification was used to describe the locations of the various palm and foot patterns. Twenty-two out of the 24 embryos showed dermatoglyphic deviations that correlated well with the cytogenetic diagnosis. The fetuses had the following disorders: 7 with trisomy 21, 2 with trisomy 18, 2 with trisomy 13, 3 with structural autosomal aberrations and 10 had a sex-chromosome aberration.

Data from a chromosome examination of 5,049 consecutive newborn children are presented. Major chromosome abnormalities were found in 43 (0.85 %) children. Only 6 of the 43 children were phenotypically abnormal to the extent that they could be diagnosed clinically; these six comprised a girl with Turner's syndrome, a boy with Patau's syndrome and four boys with Down's syndrome. It was remarkable that two male infants with karyo-types 46,XY,12p- and 46,XY/46,XY,5p- were normally developed. Chromosome variants (marker chromosomes) occurred in 87 (1.72 %) of the children. The most common marker chromosomes were Yq+, Yq-, Dp+ or Ds+ and Gp+ or Gs+ very little is known about the significance of marker chromosomes. Chromosome examination in newborn children gives the possibility of procuring incidence figures, finding families with translocations, studying segregation rates and giving genetic advice. Follow up studies of children with chromosome abnormalities and marker chromosomes compared with controls as well as treatment of children with chromosome abnormalities whenever possible are also important aspects of such studies.

Trisomy 20 mosaicism in cultured amniotic fluid cells has in only a few cases been confirmed in fetal tissue. This may lead to the assumption that the trisomic cells are of extra-fetal origin and interruption of the pregnancy is not advisable. Chromosome analysis of numerous fetal tissues indicated in two cases the presence of one or more trisomy 20 cell clones in rectum and esophagus, respectively. The clinical significance of trisomy 20 mosaicism in single organs remains to be elucidated. Besides the karyotype, genetic counselling should take into account all accessible information of the pregnancy, e.g. ultra-sound, serum alpha-fetoprotein values and obstetrical history.

Three cases of trisomy 20 mosaicism in amniotic fluid cell cultures are described. Two of the pregnancies resulted in normal full-term infants. The third pregnancy was terminated and revealed a phenotypically normal fetus. A review of five previously reported cases is presented. Explanations of these findings include in vitro nondisjunction, culture of extraembryonic tissue, and true fetal mosaicism. The diagnostic dilemma this presents is discussed.

Four different balanced X/autosome translocations: 46,X,t(X;9)(p11;q13); 46,X,t(X;12) (p11;q12); 46,X,t(X;15)(q12;p11) and 46,X,t(X;19)(q26;p12) are described in four female patients. The effect of X/autosome translocations on physical and sexual development of these women and their offspring is discussed.

The centromeric banding pattern of chromosomes 19 exhibited considerable variation. The variants were present in the majority of cells from an individual and consisted of additional dark-staining areas. There was no abnormal phenotypic effect associated with any variant and it is concluded that these additional dark-staining areas do not contain any functional genes.

Trisomy for the long arm of chromosome 20 is described in a severely affected 11-month-old girl. Her mother is heterozygous for a balanced t(16;20) translocation.

Trisomy for an F-like chromosome with banding characteristics of chromosome 20 was observed, respectively, in 25 and 8% of amniotic fluid cell clones in two cases of prenatal diagnosis for advanced maternal age. No such aneuploidy was found upon examination of fetal or postnatal tissues. In both instances there were no detectable malformations. It is suggested that propensity to nondisjunction for an F-like chromosome, not unlike tetraploidy, might be another characteristic of amniotic fluid cells in culture.

During a 3-year period a total of four boys with sex chromosome abnormalities was found among a total of 157 boys admitted to a child psychiatric hospital, giving an incidence of 2.6 % compared with the expected 0.3 % from studies in newborn populations (P (Fisher) = 0.0048). The incidence of chromosome abnormalities in the 71 girls admitted to the hospital during the 3-year period and among all 514 out-patients was not higher than expected. The frequency of chromosome variants in a 1-year incidence study of 240 children was 10.4 % compared with 1.7% among 5,049 newborn Danish children (α2= 83.539, P< 0.001). The two types of marker chromosomes found to a significantly higher extent than in the newborn population were enlarged satellites on a G chromosome and large Y. Our findings indicate that children with these marker chromosomes may have an increased risk of mental disorders.

To correlate the presence of chromosome 1p/19q deletion with the expression of R132H mutant IDH1 status in oligodendroglial tumors, and to explore molecular markers for predicting chemosensitivity of oligodendroglial tumors.The study included 75 oligodendroglial tumors (38 oligodendrogliomas and 37 oligoastrocytomas). Immunohistochemistry was used to detect the expression of R132H mutant IDH1 protein, and fluorescence in situ hybridization (FISH) was employed to detect 1p/19q deletion.Deletion of chromosome 1p and/or 19q was detected in 37 cases (37/75, 49.3%), among which co-deletion of 1p and 19q was seen in 34 cases (closely correlated, P0.01). Oligodendrogliomas WHOIIhad a slightly higher deletion rate than oligodendrogliomas WHO III, although without statistical significance. Oligodendrogliomas WHO IIand WHO III had a significantly higher deletion rate of chromosome 1p/19q than oligoastrocytomas WHO II and WHO III (P0.05). While combined loss of 1p/19q was always detected in oligodendrogliomas when FISH was positive, isolated 1p or 19q deletion was only found in oligoastrocytomas. The expression of R132H mutant IDH1 was detected in 51 of 75 cases (68.0%), in which oligodendrogliomas had a higher positive rate than oligoastrocytomas. Statistical analysis demonstrated a significant correlation between the expression of R132H mutant IDH1 protein and the presence of combined 1p/19q deletion in oligodendrogliomas (P0.05).A significant correlation was observed between the expression of R132H mutant protein and 1p/19q LOH.Expression of 132H mutant IDH1 protein is the potential biomarker for predicating the presence of 1p/19q deletion in oligodendrogliomas.

Both genes and the environment contribute to PCOS. Obesity, exacerbated by poor dietary choices and physical inactivity, worsens PCOS in susceptible individuals. The role of other environmental modifiers such as infectious agents or toxins are speculative. Phenotype confusion has characterized genetic studies of PCOS. Although several loci have been proposed as PCOS genes including CYP11A, the insulin gene, the follistatin gene, and a region near the insulin receptor, the evidence supporting linkage is not overwhelming. The strongest case can be made for the region near the insulin recept or gene (but not involving this gene), as it has been identified in two separate studies, and perhaps most importantly has not yet been refuted by larger studies. However, the responsible gene at chromosome 19p13.3 remains to be identified. To date, no gene has been identified that causes or contributes substantially to the development of a PCOS phenotype.

Objective To further evaluate the role of chromosomal translocation (15;19) in the presentation of the carcinoma (CA) of the upper aerodigestive tract. Study design and setting A retrospective study at a tertiary care pediatric medical center. Results Seven patients with a mean age of 12 years presented with CA of nasopharynx (N = 2), sinonasal region (N = I), parotid gland (N = 2), or larynx (N = 2). Treatments included combinations of surgery (N = 5), chemotherapy (N = 5), and radiation therapy (N = 4). One patient with sinonasal CA and one patient with laryngeal CA had chromosomal translocation (15;19); these patients both died of their disease with a mean survival of 6 months. The 5 patients without translocation (15;19) responded well to treatment and are disease-free with a mean follow-up of 47 months. Conclusion The preliminary results appear to indicate poor prognosis associated with the presentation of chromosomal translocation (15;19) despite aggressive multi-modality treatment. Further investigation is needed to better understand the cause and relationship of the translocation (15;19) and aggressive behavior of these tumors.

Complete triploidy was found in lymphocyte cultures From a stillborn full-term female infant with a birthweight of 1,000 g. The child had B ventricular septal detect of the heart hut no other macroscopic internal or external malformations. The mother, who had a history of prolonged anti-asthmatic medication, displayed a high incidence of satellite associations and chromatid breakages in her cultured lymphocytes. The possibility that such changes are instrumental in the formation of triploid zygotes is discussed.

The present paper reports the concurrence of Myotonic Dystrophy and an autosomal balanced translocation t(2;20)(p21;q11), both occurring de novo in a 21-year-old female.

The CAS (cellular apoptosis susceptibility) gene is the human homolog of the yeast chromosome segregation gene CSE1. CAS may have a dual function in mammalian cells, one in apoptosis and another in cell proliferation. We have now mapped the CAS gene to chromosome 20q13. This region is known to harbor amplifications that correlate with aggressive breast cancer. Southern hybridizations with a CAS cDNA fragment and fluorescent in situ hybridization (FISH) with a P1 clone containing the CAS gene show elevated copy numbers in one leukemia, three of four colon, and in three of seven breast cancer cell lines. Elevated CAS copy number in CEM leukemia and COLO201 colon cancer cells was attributable to additional copies of chromosome 20. In SW480 and COLO205 colon cancer cells CAS is part of aberrant chromosomes containing large parts of 20q. In breast cancer cells CAS is also part of aberrant 20q chromosomes (MDA-MB-157 and UACC-812) or of additional 20q isochromosome in MDA-MB-134. In MDA-MB361 and BT-474 breast cancer cells CAS is separated from other markers centromeric and telomeric of CAS on 20q. MDA-MB 361 contains one additional copy of CAS, separated from the centromeric 20q control probe. BT-474 cells have up to 12 additional CAS copies that we separated from nearby telomeric and centromeric probes on 20q and that are translocated to abnormal chromosomes.

Studies in animal models and patients with epilepsy have suggested that basal ganglia circuits may control epileptic seizures and that striatal dopaminergic transmission may play a role in seizure modulation and interruption. Chromosome 20 [r(20)] syndrome is a well-defined chromosomal disorder characterized by epilepsy, mild-to-moderate mental retardation, and lack of recognizable dysmorphic features. Epilepsy is often the most important clinical manifestation of the syndrome, with prolonged episodes of nonconvulsive status epilepticus suggesting dysfunction in the seizure control system. We present the ictal blood oxygen level-dependent (BOLD) changes in brief seizures recorded by means of electroencephalography-functional magnetic resonance imaging (EEG-fMRI) coregistration in a patient with [r(20)] syndrome. We observed ictal BOLD increments in a cortical-subcortical network involving substantia nigrastriatum and frontal cortex. At present, this is the first functional neuroimaging evidence of the involvement of the nigrostriatal system during ictal EEG discharges in [r(20)] syndrome supporting a role of the basal ganglia circuits in human epileptic seizures.

Increasing evidence supports an association between obstructive sleep apnoea (OSA) and metabolic syndrome (MeS) in both children and adults, suggesting a genetic component. However, the genetic relationship between the diseases remains unclear. We performed a bivariate linkage scan on a single Filipino family with a high prevalence of OSA and MeS to explore the genetic pathways underlying these diseases. A large rural family (n = 50, 50% adults) underwent a 10-cM genome-wide scan. Fasting blood was used to measure insulin, triglycerides, total cholesterol and high density lipoprotein (HDL) cholesterol. Attended overnight polysomnography was used to quantify the respiratory disturbance index (RDI), a measure of sleep apnoea. Body mass index z-scores and insulin resistance scores were calculated. Bivariate multipoint linkage analyses were performed on RDI and MeS components. OSA prevalence was 46% (n = 23; nine adults, 14 children) in our participants. MeS phenotype was present in 40% of adults (n = 10) and 48% of children (n = 12). Linkage peaks with a logarithm of odds (LOD) score3 were demonstrated on chromosome 19q13.4 (LOD = 3.04) for the trait pair RDI and HDL cholesterol. Candidate genes identified in this region include the killer cell immunoglobulin-like receptor genes. These genes are associated with modulating inflammatory responses in reaction to cellular stress and initiation of atherosclerotic plaque formation. We have identified a novel locus for genetic links between RDI and lipid factors associated with MeS in a chromosomal region containing genes associated with inflammatory responses.

Colorectal cancer is common, accounting for nearly 10% of all cancers. Transforming growth factor-β1 (TGF-β1) is a pleiotropic cytokine that has been implicated in the pathogenesis of colorectal neoplasia. The most studied -509CT polymorphism of TGF-β1 gene has been associated with various kinds of cancer. This study investigated the association between this genetic variant and the risk and/or progression of colorectal cancer.A case-control study was carried out of 150 colorectal cancer cases and 503 healthy controls. DNA was extracted from blood cell nuclear materials, and -509CT polymorphism in the TGF-β1 gene promoter was genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Colorectal cancer tissues (n = 70) were obtained from the studied cases for measurement of TGF-β1 mRNA expression levels. We also assessed the plasma TGF-β1 levels of cases (n = 88) and healthy subjects (n = 120).The TGF-β1 producer genotype, -509TT, was not associated with an increased risk of colorectal cancer compared with other genotypes. Colorectal cancer patients especially those with a more aggressive disease behaviour were more frequently associated with C allele.The results suggest that TGF-β1 -509CT polymorphism is not associated with either an increased risk or progression of colorectal cancer.

The authors report the first Thai family with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) in which the family members had a classical history of progressive vascular dementia. The proband was a 31-year old Thai male who presented with an acute stroke in the subcortical region. His past history revealed mental disturbance, including poor judgement and regressive behavior as well as mood changes for 1 year. He did not have a history of migraine or any other vascular risk factors except for a strong family history of ischemic stroke and progressive dementia. Magnetic resonance imaging demonstrated multiple small infarctions in the subcortical white matter of the bilateral frontal, parietal and occipital lobes with another small lesion in the pons. Genetic study demonstrated a Notch 3 mutation consisting of the substitution of a nucleotide at position 406 in exon 3 leading to the replacement of an Arginine by Cysteine at position 110 in the 2nd EGF motif, which is compatable with CADASIL.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a rare adult-onset inherited arterial disease with a distinctive neuropathological phenotype. Owing to its recent identification and variable mode of presentation, the disease is often misdiagnosed. The CADASIL gene is Notch 3 and has been mapped on chromosome 19q12 in several unrelated families. Knowledge of the phenotypic range of CADASIL, however, remains incomplete. Clinical, pathological radiological, and genetic findings in the first known Danish CADASIL pedigree are presented. Genetic testing confirmed a Notch 3 mutation. The mutation consisted of the substitution of a nucleotide at position 475 leading to the replacement of amino acid arginine for cysteine at position 133 in the third EGF motif.

In order to investigate genomic imbalances, comparative genomic hybridization was applied to 20 malignant fibrous histiocytomas. Deletions were rare and found mainly in chromosomes 2q33-35, 4q32-qter, 8p, 9p21-pter, 12p and 19p, whereas, over-representations frequently affected chromosomes 3, 4q31, 5p, 6, 7, 14q22-ter, 18p, as well as, five distinct amplifications within the regions 12q12-15 and 15q24-qter. The total number of genetic imbalances per tumor was slightly increased in primary tumors when compared to relapses. No relationship was found between the patterns of gain and loss when compared to the histological subtype, tumor grading, the clinical outcome and the p53 mutation status.

About 20% of all human conceptuses are estimated to be trisomic and trisomy of all chromosomes remains a common cause of early fetal loss. Uniparental disomy (UPD) has been reported for most human chromosomes and may be an underrecognized contributor to embryonic lethality. To investigate the contribution of UPD to spontaneous abortions, we devised a genome-based screening strategy to identify holochromosomic UPD in 18 fetal losses. No cases of UPD were identified using this approach. Based on our data, UPD does not appear to be a significant contributor to early embryonic lethality. The results of the study are presented along with a review of the cases of UPD reported in the literature by chromosome, parental origin, mode of ascertainment, and phenotypic consequences due to imprinting.

Allelic loss is a hallmark of tumor suppressor gene (TSG) inactivation. We have allelotyped 29 paired lymphoblastoid and lung cancer cell lines derived from 11 patients with small cell (SCLC) and 18 patients with non-small cell lung carcinomas (NSCLC). Statistical analysis indicated that a threshold of 30% separated non-random allelic loss from the random genetic deletions of malignancy. We have identified non-random allelic loss at 42 of 54 (78%) specific chromosomal regions examined, with 22 regions (52%) common between the two major lung cancer histologic types. There were 3 regions (7%) with allelic loss specific for SCLC and 17 regions (41%) specific for NSCLC. Furthermore, there were significant differences in loss of heterozygosity (LOH) frequencies between NSCLC and SCLC at 13 regions on eight chromosome arms (3p, 5q, 6q, 9p, 10q, 11p, 13q, and 19p). Eight homozygous deletions were present in seven cell lines at four regions, 3p12, 3p14.2, 9p21, and 10q23-25. We have also identified novel sites of chromosomal deletions. In particular, there was frequent loss at 11p13 in SCLC and loss at 6p21.3 and 13q12.3 in NSCLC. In this study, we demonstrate that a) non-random allelic losses in lung cancer involve multiple regions; b) some losses are common to both NSCLC and SCLC subtypes, whereas others are subtype specific; c) there are genetic deletions at novel chromosomal regions; and d) several homozygous deletions have been noted. Our studies demonstrate the usefulness of continuous cell lines for detailed allelotyping, for comparing genetic abnormalities between SCLC and NSCLC, and for identifying homozygous deletions.

A case of congenital cystic adenomatoid malformation of the lung diagnosed during pregnancy with, echography in a foetus 19.4 weeks old is reported. The ACP is to be included among the most rare malformations, but even rarer is the prenatal diagnosis. It must to be noted that the previous child of the same couple was also found to be affected by a malformation of the lungs. Through a genetic study of the family it was discovered that both children and the father were carriers of the same morphological chromosomic variation. The authors report the case.

This article considers the emerging research on Alzheimer disease (AD) genetics in relation to ethical questions surrounding presymptomatic and prenatal genetic testing. Given the rapid advance in AD genetics over the past 8 years, it is likely that the attention of clinicians and ethicists will increasingly turn to genetic issues. After a survey of current genetic knowledge, this article addresses 3 areas of likely ethical concern. While AD genetic screening programs are currently rare and restricted to specific pedigrees, they will become more common in the future. It is, therefore, imperative that society and clinicians begin to consider the ethical issues this raises.

Families segregating for PEPD were investigated for linkage between PEPD and APOC2. The results provide evidence for close linkage between PEPD and APOC2 in males.

A familial pericentric inversion of chromosome 19 was detected prenatally in a young primagravida. As far as the authors are aware there are no previous published reports of this rare abnormality being ascertained in this manner. The problems of counselling such a family are considered.

A patient with triplication of all of chromosome arm 20p is presented to illustrate the relatively modest degree of developmental delay that can result from autosomal triplication and the role of nondisjunction as a mechanism for deriving a partial triplication status.

A patient is shown to have acute granulocytic leukemia, bone marrow mosaicism, and cutaneous fibroblast mosaicism for trisomy 8, an inherited reciprocal translocation involving the short arms of chromosomes 7 and 20, and a family history of cancer. A normal sister who had the same balanced chromosome translocation was evaluated for a preleukemic state; the results were unremarkable. The inherited translocation and postzygotically derived trisomy 8 are thought to represent additive factors contributing to the development of leukemia in the patient.

A patient with chronic myelogenous leukemia (CML) had a Philadelphia chromosome (Ph') [t(9q+;22q-)] in all cells and trisomy C in 13% of cells (later determined to be trisomy 8) at the time of diagnosis. After 21 months of intermittent treatment with busulfan, the acute phase developed with the appearance of an additional abnormality (trisomy ? 19). During a complete remission and reconversion to the chronic phase, trisomies 8 and ? 19 DISAPPEARed, although the Ph' remained. Following a period of marked thrombocytosis, a second relapse occurred with the reappearance of both marker chromosomes.

Summary Segregation data on LW in families of informative males show that the LW (Landsteiner-Wiener) blood group locus is closely linked to the complement C3 locus and to the locus for the Lutheran blood group. This finding also confirms the presence of a larger linkage group on chromosome 19, including now the loci for apoE, Le, C3, LW, Lu, Se, H, PEPD, myotonic dystrophy (DM), neurofibromatosis (NF) and familial hypercholesterolemia (FHC). Linkage of LW with the Lewis blood group locus could not be definitely established by the present family data, but small positive scores between LW and Le suggest that the Le locus is situated outside the C3-LW region.

Linkage has been described between the loci for apolipoprotein E (apoE) and the complement C3 (C3) on chromosome 19. C3 is known to belong to a linkage group with gene order C3-Se-Lu. The present study revealed linkage between Se and apoE with peak lod score +3.3 at recombination fraction 0.08 in males and +1.36 at 0.22 in females, and linkage between apoE and Lu with lod score +4.52 at zero recombination in sexes combined. The C3-apoE linkage gives lod score +4.00 at $$\hat \Theta$$ = 0.18 in males, but +0.04 at $$\hat \Theta$$ =0.45 in females. Triple heterozygote families confirm that apoE is on the Se side and on the Lu side of C3. Allelic association between apoE and Lu has not been ruled out. Combining our data with published data on C3-Se and Se-Lu, this segment of chromosome 19 has an average sex ratio of female/male recombination of 2.3.