Sister chromatid exchange and proliferation pattern in stimulated lymphocytes of cutaneous malignant melanoma patients

Sister chromatid exchange (SCE) and the proliferative pattern of phytohemagglutinin-stimulated lymphocytes were examined in 36 nonfamilial cutaneous malignant melanoma (CMM) patients. One close relative of each of 27 CMM patients was also examined. All the patients had undergone surgical treatment for the neoplasm, but had received no chemotherapy or radiotherapy. The SCE rates were found to be higher and more variable in a significant fraction of CMM patients, and in relatively fewer unaffected relatives, which is in contrast to findings in unrelated subjects taken as controls. Also, variable and higher proportions of cells in metaphase of the first cell cycle (M1), after 72-hr culture in the presence of bromodeoxyuridine, were more often found among the CMM patients than in the controls; however, no effect of clinical progression of the neoplastic disease on SCE rates or on the lymphoproliferative pattern was observed. The present study indicates heterogeneity among subjects who develop CMM and suggests that the peculiarities of SCE rates and of the lymphoproliferative patterns observed in some of the CMM patients and in a few of their close relatives may be connected with the mechanism of onset of the neoplasm.     

Ultraviolet-induced formation of micronuclei and sister chromatid exchange in cultured fibroblasts of patients with cutaneous malignant melanoma

Genetically enhanced sensitivity to ultraviolet (UV) radiation may play an important role in the development of cutaneous malignant melanoma (CMM). This was studied in cultured fibroblasts of 26 CMM patients and controls by micronucleus (MN) test and sister chromatid exchange (SCE) after UV irradiation (375 J/m2). Sister chromatid exchange and MN formation were used as parameters to detect the UV-induced genotoxic damage in the individual cell strains. We found that the UV-induced level of MN was significantly increased in CMM patients (p = 0.0005), being most pronounced in the familial cases (p = 0.0001). Ultraviolet-induced SCE was also elevated in CMM patients (p = 0.001), but there was no difference between familial and nonfamilial cases. The present findings indicate that genetic predisposition contributes to the development of CMM in a subset of CMM patients and may be due to an enhanced susceptibility to UV light.     

CDKN2A mutations in Spanish cutaneous malignant melanoma families and patients with multiple melanomas and other neoplasia

The CDKN2A gene has been implicated in cutaneous malignant melanoma (CMM) in about 40% of families with linkage to chromosome 9p21, while a small proportion of families have mutations in the CDK4 gene. In order to estimate the importance of these genes in the predisposition to CMM in Spanish families and patients we have analysed, by SSCA, a total of 56 subjects belonging to 34 CMM families, and nine patients with multiple CMM and other neoplasia. We have detected germline CDKN2A mutations in six out of the 34 families (17%). A frameshift mutation (358delG) and four missense mutations (G59V, G101W (two cases), D84Y, and R87W) were identified. Five CMM patients from different families (14%) carried the A148T variant, which is known not to affect p16 activity. No mutations were detected in the patients with multiple CMM or other neoplasms. We have not found mutations either in exon 1 beta of the CDKN2A gene or in exon 2A of CDK4. Linkage analysis of the 9p21 region showed exclusion for one of the families for CMM and for four families for CMM/dysplastic naevi. This study indicates a small role for CDKN2A in Spanish CMM families and suggests that other genes are also responsible for CMM predisposition.     

Sister chromatid exchange: Variation by age,sex, smoking,and breast cancer status

Variation in sister chromatid exchange (SCE) frequency in lymphocytes of 125 persons was compared using a multivariate general linear model. The study was performed to determine whether SCE frequency differs with respect to age, sex, smoking, and breast cancer status. Study subjects were divided into: members of two branches of families having an excess of cancer (primarily breast) including a brother and sister in one family who developed nonbreast malignancies within 1 yr of the study; women in both families successfully treated for breast cancer (all at least 5 yr posttreatment); and women from the general population with confirmed breast cancer.Controls consisted of spouses who married into the high-risk kindreds, hospital personnel, and others (primarily tradesmen without history of occupational exposure). Results show that: (1) Women with active breast cancer have a significantly higher mean SCE frequency than control women or women greater than 5 yr posttreatment for breast cancer; (2) Cigarette smokers show a significantly higher number of SCEs than was observed in nonsmokers; (3) The increase in SCE level in smokers is dose-related to exposure as measured by cumulative pack-years; (4) SCE values in both high-risk families are not significantly different from controls; (5) Neither the age nor sex of the individual affects SCE frequency; and (6) The observed distribution of exchanges agrees with that expected based on the proportion of the genome represented by each chromosome group.     

In vitro hyperdiploidy in a family with nasopharyngeal cancer

In this in vitro study of 28 members of a family with nasopharyngeal cancer (NPC) and nasopharyngeal angiofibromas (NPA) in consecutive generations, in vitro hyperdiploidy, (IVH) in dermal fibroblast cultures was associated with NPC in 2 affected members, NPA in 4 affected members, and 4 of 16 members considered to be at increased genetic risk for these tumors. None of the six controls, all spouses, had IVH. As IVH has been shown to be associated with high specificity (approximately 99%) with other heritable single tumors, IVH appeared to be a potential biomarker also for genetic predisposition for NPC. As NPC and NPA did not occur in a single affected family member, any association other than with IVH has not been established. IVH may be the in vitro expression of a gene/genes conveying tumor proneness per se, or it may determine tissue specificity of tumor pathology. As cellular hyperdiploidy has been considered to convey genomic instability, chromosome instability in numerically normal (diploid) and altered (tetraploidy and hyperdiploid) dermal fibroblasts from two NPC-affected members and two control spouses were evaluated by a parameter of chromosome stability--the frequency of sister chromatid exchanges (SCE) per cell. Irrespective of donor source, the diploid and tetraploid fibroblasts exhibited little evidence of chromosome instability, whereas there was a statistically significant difference in the mean frequency of SCE/cell between hyperdiploid and diploid cells in cultures derived from NPC-affected members (p less than 0.01).     

High prevalence of germline CDKN2A mutations in Slovenian cutaneous malignant melanoma families

Aim

To prospectively determine the prevalence of germline CDKN2A mutations in the Slovenian cutaneous malignant melanoma (CMM) families.

Methods

From January 2001 till the end of 2003 we prospectively screened 19 individuals from 11 CMM families, as well as 3 children with CMM aged from 6 to 13 years, with a negative family history.

Results

Five distinct mutations were detected in 5 out of 11 screened families (10/19 individuals) and a previously recognized polymorphism was detected in a single family. Detected mutations were functionally deleterious (T281A, G68A, G301T, G71C and IVS – 1g > a). No mutations could be detected in 3 children.

Conclusions

The prevalence of CDKN2A mutations among Slovenian CMM families was high, indicating the need for genetic counseling.The CDKN2A gene is the most common cause of inherited cutaneous malignant melanoma (CMM) (1). The presence and frequency of CDKN2A gene mutations in familial CMM vary considerably in different populations. Yakobson (2) did not find even a single case of germline CDKN2A mutation among 31 Israeli CMM families. However, Mantelli (3) reported a high prevalence of 34% of the germline CDKN2A mutations in his study of 62 Italian CMM families. Overall, the CDKN2A mutations were detected in approximately 20% of the tested CMM families (1).The aim of our study was to prospectively determine the prevalence of germline CDKN2A mutations in the Slovenian CMM families.     

Sister chromatid exchanges, hyperdiploidy and chromosomal rearrangements studied in cells from melanoma-prone individuals belonging to families with the dysplastic nevus syndrome

Cytogenetic investigations were performed on 25 individuals belonging to six melanoma-prone families with multiple melanocytic lesions (the dysplastic nevus syndrome, DNS). Patients having DNS with or without a history of melanoma were compared with clinically normal relatives and unrelated normal controls. The results indicate normal frequencies of hyperdiploidy and spontaneous sister chromatid exchanges in the fibroblasts of all individuals studied. Karyotypic analyses were carried out on the members of one family. The patients with DNS had a normal constitutional karyotype. In lymphocytes or fibroblasts from five patients, however, increased frequencies of cells with random chromosomal rearrangements were observed. These abnormalities, mainly translocations and inversions, were not found in two of the patients' spouses and in six clinically normal relatives. In the fibroblast cultures considerable clonal selection of cytogenetically abnormal cells occurred.     

Deficiency of galactosylhydroxylysyl glucosyltransferase, an enzyme of collagen synthesis, in a family with dominant epidermolysis bullosa simplex

Members of a family with dominant epidermolysis bullosa simplex were found to have a deficiency of galactosylhydroxylysyl glucosyltransferase (GGT), an enzyme catalyzing the glucosylation of galactosylhydroxylysyl residues in the biosynthesis of collagen. The enzyme's activity was low in serum, skin tissue, and cultured skin fibroblasts, although no abnormality was found in three other intracellular enzymes of collagen biosynthesis. Mixtures of serum samples from patients and healthy controls gave the expected GGT activity, indicating that the low values were not due to inhibitors. GGT deficiency was accompanied by decreased product formation in vivo, as shown by a markedly decreased urinary excretion of glucosylgalactosylhydroxylysine. Six of 12 affected members had definite GGT deficiency, and five had some evidence suggestive of this abnormality; 13 of 15 unaffected members had no such manifestations. No similar GGT deficiency was found in three other families with the same disease. We conclude that GGT deficiency may be etiologically related to this disease in some families, but that different defects must be the cause in other cases.     

Elevated sister chromatid exchange and cell cycle analysis in bone marrow in childhood ALL

Sister chromatid exchange (SCE) frequencies were analyzed in both stimulated and unstimulated bone marrow samples from eight patients recently found to have childhood acute lymphocytic leukemia (ALL). Six of the patients had elevated SCE frequencies in stimulated marrow when compared to control values. In unstimulated marrow, all four patients had elevated SCE frequencies. These data agree with peripheral leukocyte findings in ALL. Cell cycle analysis revealed no significant differences between the patient marrows and the control marrows. Since no correlation between cell cycle distribution and SCE frequency was found, it is suggested that the differences in SCE observed may be related to the type of proliferating cell.     

BAP1 cancer syndrome: malignant mesothelioma, uveal and cutaneous melanoma, and MBAITs

ABSTRACT: BACKGROUND: BRCA1--associated protein 1 (BAP1) is a tumor suppressor gene located on chromosome 3p21. Germline BAP1 mutations have been recently associated with an increased risk of malignant mesothelioma, atypical melanocytic tumors and other neoplasms. To answer the question if different germline BAP1 mutations may predispose to a single syndrome with a wide phenotypic range or to distinct syndromes, we investigated the presence of melanocytic tumors in two unrelated families (L and W) with germline BAP1 mutations and increased risk of malignant mesothelioma. METHODS: Suspicious cutaneous lesions were clinically and pathologically characterized and compared to those present in other families carrying BAP1 mutations. We then conducted a meta-analysis of all the studies reporting BAP1-mutated families to survey cancer risk related to the germline BAP1 mutation (means were compared using t-test and proportions were compared with Pearson Chi2 test or two-tailed Fisher's exact test). RESULTS: Melanocytic tumors: of the five members of the L family studied, four (80%) carried a germline BAP1 mutation (p.Gln684*) and also presented one or more atypical melanocytic tumors; of the seven members of W family studied, all carried a germline BAP1 mutation (p.Pro147fs*48) and four of them (57%) presented one or more atypical melanocytic tumors, that we propose to call "melanocytic BAP1-mutated atypical intradermal tumors" (MBAITs). Meta-analysis: 118 individuals from seven unrelated families were selected and divided into a BAP1-mutated cohort and a BAP1-non-mutated cohort. Malignant mesothelioma, uveal melanoma, cutaneous melanoma, and MBAITs prevalence was significantly higher in the BAP1-mutated cohort (p [LESS-THAN OR EQUAL TO] 0.001). CONCLUSIONS: Germline BAP1 mutations are associated with a novel cancer syndrome characterized by malignant mesothelioma, uveal melanoma, cutaneous melanoma and MBAITs, and possibly by other cancers. MBAITs provide physicians with a marker to identify individuals who may carry germline BAP1 mutations and thus are at high risk of developing associated cancers.     

Coping with Pediatric Leukemia: A Two-Year Follow-Up

Sixty families of children with acute leukemia who participatedin a prospective study of family coping were assessed at 2 yearspostdiagnosis. A wide variety of coping behaviors was found.According to ratings made by physicians, nurses, psychosocialstaff, and themselves, most of the families were coping well.Parents' scores on the Summed Coping Scale of the CPI were generallywithin the normal range. Variables which correlated significantlywith coping at 2 years postdiagnosis were quality of the maritaland family relationship, previous coping with the illness, copingof other family members, adequacy of support system, lack ofadditional stresses, open communication within the family, andan attitude of living in the present. Although it had been effectivefor mothers in earlier phases of the illness, psychosocial interventionwas not significantly related to coping at this time, when mostof the children were in remission and doing well medically.     

Establishment of B-lymphoid cell lines retaining cytogenetic characteristics of Bloom syndrome

The present study describes the establishment of and chromosomal changes in B-lymphoid cell lines from cells of Bloom syndrome (BS) patients using Epstein-Barr virus (EBV). Even though PHA-stimulated BS lymphocytes from all five patients studied showed high levels of sister chromatid exchange (SCE), three EBV-transformed BS-B-lymphoid cell lines had normal levels of SCE and two yielded two types of cell populations, i.e., one with increased SCE and chromosome instability (including breaks and quadriradials) and another with normal levels of SCE and without structural aberrations. The karyotypic abnormalities, as observed in the BS lines have not been seen in the cells of any established normal B-lymphoid lines transformed by EBV and strongly suggest that the chromosome abnormalities in the BS--B-cell lines with abnormal karyotypes originated in vivo and not through an in vitro effect of EBV. Furthermore, in the EBV-transformed B-cell lines, we found quadriradial formation between sister chromosomes during endomitoses instead of between homologous chromosomes, strongly suggesting that quadriradial formation may be closely related to SCE. The coexistence in BS subjects of abnormal and normal populations of cells with respect to the number of SCE awaits explanation.     

Hexosaminidase A deficiency in adults

Deficiency of hexosaminidase A (Hex A) in adults was found in 15 individuals from nine unrelated Ashkenazi families; 14 individuals had neurological symptoms, one was clinically intact. Clinical, biochemical and genetic findings are reported and compared to previously reported cases. The clinical picture varied between and within families and included spinocerebellar, various motor neuron and cerebellar syndromes. Psychosis appeared in 30% of cases. Involvement of three generations was recorded in one family. The phenotype appears too variable to serve as a basis for genetic classification. The level of Hex A activity in serum, leukocytes, and fibroblasts of all 14 patients was in the range of Tay-Sachs disease (TSD) homozygotes when measured by the routine heat-inactivation method. More sensitive and direct methods detected some residual activity. Cultured skin fibroblasts of patients synthesize the alpha and beta chain precursors of Hex A of the same molecular weight as that synthesized by normal fibroblasts. However, the amount of the alpha chain precursor is greatly reduced. Mature chains were not detected. The one healthy adult we studied displayed a nonuniform distribution of Hex A; while it lacked activity in the serum it had intermediate activity in fibroblasts and leukocytes.     

Spiradenocylindromas of the skin: Tumors with morphological features of spiradenoma and cylindroma in the same lesion: Report of 12 cases

Twelve cases of spiradenocylindromas, which revealed features of both spiradenoma and cylindroma in the same tumor mass, are presented. Nine female patients had multiple neoplasms occurring mostly on the scalp, and two female and one male patient had a solitary cutaneous lesion. Three of the female patients with multiple cutaneous tumors had a familial history of similar cutaneous neoplasms. In one of the patient's family, the multiple cutaneous tumors were known to occur in multiple family members in four consecutive generations. One patient with multiple cutaneous lesions was known to have associated multiple kidney cysts as confirmed by computed tomography. Histologically, spiradenocylindromas are composed of intermixed areas that are either of typical spiradenoma in appearance or of typical cylindroma appearance. Apocrine and trichoepitheliomatous differentiation seen in two cases in the present series points to spiradenomas, as well as cylindromas, having complex hair follicle (folliculo-sebaceous apocrine) rather than eccrine differentiation. The presence of lymphoid tissue was a histological feature in the present series, which was prominent in all the spiradenomatous parts of the tumors and which was scanty or practically absent in all the cylindromatous parts. The selective presence of lymphocytes in spiradenoma and an absence in cylindroma suggest that spiradenomas have the unique property of attracting lymphocytes. The malignant tumors arising in three patients in the present series had the morphology of a poorly differentiated epithelioid neoplasm. Three patients died of the disease and the other patients were either free of disease or alive with disease 1-30 years on follow up.     

Familial papillary carcinoma of the thyroid

Of 226 consecutive papillary carcinoma patients, 14 indicated that at least one other relative was similarly affected. Pathology confirmation was obtained in 8 of the 14 families. Of the eight families with documented familial papillary carcinoma, one had five members, another had four members, and yet another had three members affected. The remaining families had two members affected. In those families with two or more persons with confirmed papillary carcinomas of the thyroid, 20 first- and second-degree relatives were examined. Of those, one had a previously unidentified papillary carcinoma and 6 had a benign thyroid disease (4 primary hypothyroidism and 2 simple goiters). High-resolution chromosome studies of four patients from four different families were normal, and there was no increase in chromosome breakage in a fifth patient from yet another family. Autosomal dominant inheritance is possible. Although there was no family history of lipomas, osteomas, or intestinal polyposis to suggest Gardner syndrome, four parents of our familial papillary carcinoma patients had colon cancer. In addition, three other relatives died of unidentified intra-abdominal cancer. The apparently high frequency of colon cancer and other abdominal cancer in relatives was an additional concern. Based on our observations, three clinical recommendations can be made: obtain a family history of all patients with papillary carcinoma of the thyroid, since between 3.5 to 6.2% will have another affected relative; when two or more persons in a family have papillary carcinoma of the thyroid, all first- and second-degree relatives should have a neck palpation by an experienced examiner; and families with two or more persons with papillary carcinoma should be observed for possible colon cancer.     

Circulating T lymphocyte subsets in coeliac disease (CoD) patients and healthy family members

Increased proportions of circulating antigen-primed CD45RO⁺ TCR γδ cells have been found in untreated CoD patients. As certain immunological features are now found in both CoD and healthy persons carrying the HLA DQ2 heterodimer, we sought to establish whether healthy members of the families of CoD patients who are positive for HLA DQ2 and also have increased densities of TCR γδ intraepithelial lymphocytes (IEL) in their small bowel mucosa have elevated levels of circulating TCR γδ memory cells. Peripheral blood T cells were analysed by flow cytometry in 22 patients with CoD and 16 healthy family members. Untreated CoD patients had higher percentages of circulating CD45RO⁺ TCR γδ cells and CD45RO⁺ Vδ1⁺ cells than healthy family members. On the other hand, the amount of circulating Vδ1⁺ lymphocytes was lower in patients with CoD compared with healthy family members. In contrast, no differences were found between HLA DQ2⁺ and HLA DQ2^? healthy family members in respect of circulating TCR γδ cell subsets. The change in circulating TCR γδ cell subsets found in patients with CoD is thus a consequence of an ongoing immunological process which diminishes on a gluten-free diet rather than a phenomenon directly caused by DQ2. These changes in peripheral blood are not found in healthy individuals who have the same HLA alleles DQA1*0501 and DQB1*0201 encoding the HLA DQ2 and who also have increased densities of TCR γδ IEL in their otherwise normal jejunal mucosa.     

Chromosomal breakage and sister chromatid exchange in peripheral blood lymphocytes and lymphoblastoid cell lines in the X-linked lymphoproliferative syndrome

The frequencies of chromosomal aberrations and sister chromatid exchange (SCE) were measured in lymphoblastoid cell lines (LCLs) and in phytohemagglutinin (PHA)- and pokeweed mitogen (PWM)-stimulated lymphocytes from males with X-linked lymphoproliferative (XLP) syndrome, their obligate carrier mothers, and control subjects. We observed an increased frequency of chromosomal aberrations including increased polyploidy in LCLs derived from families with XLP with time in culture. The SCE rate in LCLs (mean of 3.89 SCEs per cell) was much lower than that in PHA- or PWM-stimulated lymphocytes: PWM-stimulated lymphocytes showed 9.58 SCEs per cell and PHA-stimulated cells had 11.38 SCEs per cell. A greater number of chromosomal gaps and breaks in the D-group chromosomes of LCLs of affected males and carrier females were identified compared to the number expected, based on chromosomal length and the number of aberrations seen in PHA-stimulated cell cultures. No differences in the frequency of SCEs or chromosomal aberrations were found in control subjects and affected males or carrier females in the peripheral lymphocytes stimulated by PHA. Phenotypes of XLP appear to arise from failure of immune responses to Epstein-Barr virus (EBV) and not from intrinsic chromosomal breakage or instability.     

Truncating mutations of TP53AIP1 gene predispose to cutaneous melanoma

Genetic predisposition to cutaneous malignant melanoma (CMM) involves highly penetrant predisposing genes and low and intermediate penetrant predisposing alleles. However, the missing heritability in (CMM) is still high. For such and in order to identify new genetic factors for CMM, we conducted an exome sequencing study in high‐risk CMM patients. Two rounds of exome sequencing were successively performed in 33 and 27 high‐risk patients. We focused on genes carrying rare nonsense, frameshift, and splice variants (allelic frequency <1%) that were present in both series of exomes. An extension study was then conducted in a large cohort (1 079 CMM patients and 1 230 Caucasian ethnically matched healthy controls), and the inactivating variants frequency was compared between groups using two‐sided Fisher exact test. Two TP53AIP1 truncating mutations were identified in four patients: a frameshift c.63_64insG, p.Q22Afs*81 in two patients from the same family and in the proband of a second family; and a nonsense mutation c.95 C > A, p.Ser32Stop in a patient with multiple CMMs. In all patients, TP53AIP1 truncating variants were strongly associated with CMM risk (two‐sided Fisher exact test = 0.004, OR = 3.3[1.3‐8.5]). Additionally, we showed that TP53AIP1 mRNA was strongly down‐regulated throughout different phases of melanoma progression. TP53AIP1 gene is a TP53 target which plays a key role by inducting apoptosis in response to UV‐induced DNA damage. Constitutional mutations of TP53AIP1 had previously been involved in susceptibility to prostate cancer. Our results show that constitutional truncating TP53AIP1 mutations predispose to CMM in the French population. Replication studies in other populations should be performed.     

Shared and persistent asymptomatic cutaneous human papillomavirus infections in healthy skin

Cutaneous human papillomavirus (HPV) types are commonly found in normal skin, and some of them have been suspected to play a role in the development of non‐melanoma skin cancer. This present study is divided into three sections, the aims of this study were to examine if certain HPV‐types persist over time and if HPV‐types are shared within families. From the first part of the study, swab samples from foreheads were collected for three longitudinal studies from one family with a newborn baby. Five specific HPV‐types were isolated from the family with a newborn, with HPV‐5 and FA67 being found at various time points and prevalence rates in all four members of the family. Part 2 consisted of a followed up study from two families with a 6 years interval. Six of the family members were found to have at least one of the HPV‐types identified in the family 6 years earlier. Many of the HPV‐types identified were shared within the families studied. Part 3 of this study involved weekly samples from four healthy females for 4 months. Among the four healthy individuals, 11%, 65%, and 56% of the weekly samples were HPV‐DNA positive with one individual HPV‐negative. All specimens were tested for HPV‐DNA by PCR using the broad range HPV‐type primer pair FAP59/64. The positive samples were HPV‐type determined by cloning and sequencing. Specific cutaneous HPV‐types persist over long periods of time in healthy skin in most individuals investigated and certain HPVs are shared between family members. J. Med. Virol. 81:1444–1449, 2009. © 2009 Wiley‐Liss, Inc.     

Sister chromatid exchange in malignant lymphomas

Sister chromatid exchange (SCE) was evaluated in peripheral lymphocytes from 20 untreated patients with malignant lymphomas: 6 with Hodgkin's disease (HD), 14 with non-Hodgkin lymphoma (NHL), and 5 with lymphadenitis. The mean SCE frequency (+/- SE) was: 11.2 +/- 0.6, 11.0 +/- 0.6, and 7.2 +/- 0.3 for HD, NHL, and lymphadenitis patients, respectively, and 8.7 +/- 0.2 for the control group. No differences in SCE score were observed in HD and NHL. These results allowed us to consider both groups (HD and NHL) as a single neoplastic population (mean +/- SE, 11.0 +/- 0.4). No significant differences were found between the lymphadenitis and control groups. On the other hand, significantly higher SCE scores were seen in neoplastic populations than in the control and lymphadenitis groups (p less than 0.001 and p less than 0.01, respectively). When SCE was compared by chromosome number and group between neoplastic patients and controls, a higher SCE frequency was observed in chromosomes #1, #2, #3, and B, C + X, E, F chromosome groups than in controls. SCE levels were significantly higher in lymphoma patients in all chromosome numbers and groups mentioned than in patients with lymphadenitis. It is suggested that the high SCE rate in the malignant lymphoma population is possibly related to an increased chromosomal instability.