Chromosome abnormalities in pancreatic adenocarcinoma

Adenocarcinoma of the pancreas is the fifth most common cause of cancer deaths in the United States, yet few cytogenetic studies of this tumor have been reported. We analyzed 26 primary tumors to identify which chromosome abnormalities occur most frequently in this neoplasm. One carcinoma was well differentiated and mucin producing, 18 were moderately well differentiated, and seven were poorly differentiated. Only normal karyotypes were obtained from nine carcinomas. The remaining 17 carcinomas frequently had normal metaphase cells in addition to simple to highly complex karyotypes. The modal chromosome number in 20 carcinomas was diploid or near-diploid; four carcinomas had both a major near-diploid and near-triploid or near-tetraploid component, and two were near-tetraploid. Numerical abnormalities included loss of whole copies of chromosomes 6, 17, and 18, and gains of chromosome 20. Structural abnormalities were frequent, with 1p, 2p, 3p, 4q, 6q, 7q, 1 1q, and 17p recurrently involved. Results of this study were combined with karyotypes of 19 other primary adenocarcinomas of the pancreas reported in the literature. The combined data involving 1 17 breakpoints suggest that careful analysis of chromosome 20, proximal 1 q. 6q, proximal 8p. and proximal 17p could be productive in defining genes involved in adenocarcinoma of the pancreas. Genes Chrom Cancer 9:93-100 (1994).© 1994 Wiley-Liss, Inc.     

Karyotypic characterization of urinary bladder transitional cell carcinomas

Samples from 34 primary transitional cell carcinomas (TCCs) of the bladder were short-term-cultured and processed for cytogenetic analysis after G-banding of the chromosomes. Clonal chromosome abnormalities were detected in 27 tumors and normal karyotypes in 3, and the cultures from 4 tumors failed to grow. Losses of genetic material were more common than gains, indicating that loss of tumor suppressor genes may be of major importance in TCC pathogenesis. There was no clonal heterogeneity within individual tumors, consonant with the view that TCCs are monoclonal in origin. The most striking finding was the involvement of chromosome 9 in 92% of the informative cases, as numerical loss of one chromosome copy in 15 cases, but as structural rearrangement in 8. The changes in chromosome 9 always led to loss of material; from 9p, from 9q, or of the entire chromosome. A total of 16 recurrent, unbalanced structural rearrangements were seen, of which del(1)(p11), add(3)(q21), add(5)(q11), del(6)(q13), add(7)(q11), add(11)(p11), i(13)(q10), del(14)(q24), and i(17)(q10) are described here for the first time. The karyotypic imbalances were dominated by losses of the entire or parts of chromosome arms 1p, 9p, 9q, 11p, 13p, and 17p, loss of an entire copy of chromosomes 9, 14, 16, 18, and the Y chromosome, and gains of chromosome arms 1q and 13q and of chromosomes 7 and 20. The chromosome bands and centomeric breakpoints preferentially involved in structural rearrangements were 1q12, 2q11, 5q11, 8q24, 9p13, 9q13, 9q22, 11p11, and 13p10. Rearrangements of 17p and the formation of an i(5)(p10) were associated with more aggressive tumor phenotypes. There was also a general correlation between the tumors' grade/stage and karyotypic complexity, indicating that progressive accumulation of acquired genetic alterations is the driving force behind multistep bladder TCC carcinogenesis.     

Complex karyotypes in a series of pediatric osteosarcomas

Cytogenetic analysis was performed on eight osteosarcomas, including six primary untreated biopsies, one second primary in a patient with a history of undifferentiated sarcoma, and one recurrent lung metastasis. Two primary tumors and the peripheral blood lymphocytes from all eight patients had normal karyotypes. Six of the tumors demonstrated extremely complex karyotypes, with modal numbers in the hypodiploid, triploid, and hypertetraploid ranges. The predominant types of structural abnormalities observed were nonreciprocal translocations and deletions, which differed between cases. A consistent loss of normal chromosome 13 homologs was evident in the six cases with abnormal tumor karyotypes; however, chromosomal loss was not restricted to #13. Molecular studies of osteosarcoma, especially with regard to the retinoblastoma locus on chromosome 13, should take into consideration the complex cytogenetic changes seen in this tumor.     

Chromosome analysis of 97 primary breast carcinomas: Identification of eight karyotypic subgroups

Chromosome banding analysis of 97 short-term cultured primary breast carcinomas revealed clonal aberrations in 79 tumors, whereas 18 were karyotypically normal. In 34 of the 79 tumors with abnormalities, two to eight clones per case were detected; unrelated clones were present in 27 (34%) cases, whereas only related clones were found in seven. These findings indicate that a substantial proportion of breast carcinomas are of polyclonal origin. Altogether eight abnormalities were repeatedly identified both as sole chromosomal anomalies and as part of more complex karyotypes: the structural rearrangements i(1)(q10), der(1;16)(q10;p10), del(1)(q11–12), del(3)(p12–13p14–21), and del(6)(q21–22) and the numerical aberrations +7, +18, and +20. At least one of these changes was found in 41 (52%) of the karyotypically abnormal tumors. They identify a minimum number of cytogenetic subgroups in breast cancer and are likely to represent primary chromosome anomalies in this type of neoplasia. Other candidates for such a role are translocations of 3p12–13 and 4q21 with various partner chromosomes and inversions of chromosome 7, which also were seen repeatedly. Additional chromosomal aberrations that give the impression of occurring nonrandomly in breast carcinomas include structural rearrangements leading to partial monosomies for 1p, 8p, 11p, 11q, 15p, 17p, 19p, and 19q and losses of one copy of chromosomes X, 8, 9, 13, 14, 17, and 22. The latter changes were seen consistently only in complex karyotypes, however, and we therefore interpret them as being secondary anomalies acquired during clonal evolution.     

Cytogenetic analysis of 63 non-small cell lung carcinomas: Recurrent chromosome alterations amid frequent and widespread genomic upheaval

A detailed cytogenetic analysis of 63 non-small cell lung carcinomas (NSCLCs) was carried out for identification of recurrent chromosomal alterations. Most specimens displayed very complex karyotypes with multiple numerical and structural changes (median number, 31). Losses of chromosomes 9 (65% of cases) and 13 (71%) were the most frequent numerical changes. Loss of the Y was often observed in tumors from males. Gain of chromosome 7 was also frequent (41%). Chromosome arms 1p, 1, 3p, 3q, 6q, 7q, 8q, 9p, 11q, 17p, and 19q were particularly prone to rearrangement. The chromosome arm most often contributing to losses was 9p (79%). Other arms that were frequently lost included 3p, 6q, 8p, 9q, 13q, 17p, 18q, 19p, 21q, 22q, and the short arm of each acrocentric chromosome. The percentage of cases with loss of 3p was significantly higher in squamous cell carcinomas (94%) than in adenocarcinomas (60%). There was also a statistically significant increase in the proportion of cases with gains of 1q, 7p, and 11q in adenocarcinomas compared to squamous cell carcinomas. Several recurrent isochromosomes and unbalanced exchanges were found. Among these was i(5p), which was observed in nine tumors, eight of which displayed adenomatous features. An i(8q) was identified in six cases, including five adenocarcinomas. Double minutes and/or homogeneously staining regions were seen in seven specimens. These data indicate that numerous chromosome alterations contribute to the pathogenesis of NSCLC and that, amid this widespread genomic disarray, recurrent abnormalities exist that could have biological and clinical implications.     

Karyotypic characterization of colorectal adenocarcinomas

Cytogenetic analysis of short-term cultures from 52 primary colorectal adenocarcinomas revealed clonal chromosome aberrations in 45 tumors, whereas the remaining 7 had a normal karyotype. More than 1 abnormal clone was detected in 26 tumors; in 18 of them, the clones were cytogenetically unrelated. The modal chromosome number was near-diploid in 32 tumors and near-triploid to near-tetraploid in 13. Only numerical aberrations were identified in 13 carcinomas, only structural aberrations in 3, and 29 had both numerical and structural changes. The most common numerical abnormalities were, in order of decreasing frequency, gains of chromosomes 7, 13, 20, and Y and losses of chromosomes 18, Y, 14, and 15. The structural changes most often affected chromosomes 1, 17, 8, 7, and 13. The most frequently rearranged chromosome bands were, in order of decreasing frequency, 13q10, 17p10, 1p22, 8q10, 17p11, 7q11, 1p33, 7p22, 7q32, 12q24, 16p13, and 19p13. Frequently recurring aberrations affecting these bands were del(1)(p22), i(8)(q10), i(13)(q10), and add(17)(p11–13). The most common partial gains were from chromosome arms 8q, 13q, and 17q and the most common partial losses from chromosome arms 1p, 8p, 13p, and 17p. A correlation analysis between the karyotype and the clinicopathologic features in our total material, which consists of altogether 153 colorectal carcinomas, including 116 with an abnormal karyotype, showed a statistically significant association (P < 0.05) between the karyotype and tumor grade and site. Carcinomas with structural chromosome rearrangements were often poorly differentiated; well and moderately differentiated tumors often had only numerical aberrations or normal karyotypes. Abnormal karyotypes were more common in rectal carcinomas than in carcinomas situated higher up. Near-triploid to near-tetraploid karyotypes were more than twice as frequent in tumors of the distal colon as in those of the proximal colon and rectum. The cytogenetic data indicate that carcinomas located in the proximal colon and rectum, which often are near-diploid with simple numerical changes and cytogenetically unrelated clones, probably arise through different mechanisms than do tumors located in the distal colon, which more often have complex near-triploid to near-tetraploid karyotypes.     

Promiscuous translocations of chromosome arm 17q in human neuroblastomas

Deletions of chromosome arm 1p and amplification of the MYCN oncogene are well-recognized genetic changes in neuroblastoma cells. Technical difficulties in cytogenetic analysis of this tumour have hampered the recognition of other recurring abnormalities, but recent use of molecular cytogenetic techniques has indicated significant involvement of chromosome arm 17q. In primary tumours and in cell lines, a recurrent unbalanced translocation t(1p;17q) has been identified by fluorescence in situ hybridization. We confirm the occurrence of this translocation in primary tumours and, in addition, we describe seven new structural rearrangements all of which result in gain of 17q in tumour cells. These rearrangements involved chromosome arms 9p, 10q, 11p, 14q, and 16q. Triplication of the 17q arm was seen in one case. The 17q breakpoint was most commonly q21. All these 17q changes were found in near-diploid tumours. We have also reviewed the literature for neuroblastoma karyotypes involving 17q abnormalities; taken in conjunction with our findings this indicates a remarkable promiscuity of translocation partners, with more than 20 different chromosome regions involved in 17q translocations. Genes Chromosom. Cancer 19:143–149, 1997 © 1997 Wiley-Liss Inc.     

Differentially amplified chromosome 12 sequences in low- and high-grade osteosarcoma.

Most osteosarcomas are highly aggressive malignancies characterized by a complex pattern of chromosome abnormalities. However, a subgroup of low-grade, parosteal tumors exhibits a relatively simple aberration pattern dominated by ring chromosomes carrying amplified material from chromosome 12. To assess whether sequences from this chromosome were differentially amplified in low- and high-grade osteosarcomas, copy numbers of the CCND2, ETV6, KRAS2, and D12S85 regions in 12p and the MDM2 region in 12q were evaluated by interphase or metaphase fluorescence in situ hybridization (FISH) in 24 osteosarcomas. Amplification of MDM2 was detected in all five low-grade and four high-grade osteosarcomas, all of which showed ring chromosomes. An overrepresentation of 12p sequences was found in 1/5 low-grade and in 9/19 high-grade tumors. Multicolor single-copy FISH analysis of metaphase cells from six high-grade tumors showed that extra 12p material either occurred together with MDM2 in ring chromosomes or was scattered over the genome as a result of complex structural rearrangements. Most tumors (8/10) not containing amplification of the assessed chromosome 12 loci exhibited a nondiploid pattern at evaluation with probes for centromeric alpha satellite sequences. These findings indicate that gain of sequences from the short arm of chromosome 12 could be a possible genetic pathway in the development of aggressive osteosarcoma.     

Chromosome analyses of 16 cases of Wilms tumor: different pattern in unfavorable histology

Cytogenetic analyses of 16 cases of Wilms tumor with abnormal karyotypes were reviewed, 15 cases of unilateral tumor and 1 bilateral. Three tumors exhibited an unfavorable histology (i.e., anaplastic changes); the rest fell into the favorable histology group. Of the 17 tumors with abnormal clonal aberrations, 9 tumors were hyperdiploid (53%), 7 had pseudodiploid karyotypes (41%), and 1 was hypodiploid (6%). The most common numerical aberrations in descending order of frequency were gain of chromosomes 12, 8, and 6 and loss of chromosome 16. Structural rearrangements mostly involved chromosome 1, followed by chromosomes 7, 14, and 17. Clustering of breaks around 1p22 approximately p31-->pter resulting in partial loss of 1p was the most frequent structural aberration. Additionally, i(7q) was observed as a sole abnormality in two tumors and a 7p translocation in two other tumors. Two other recurrent abnormalities were a partial deletion of 14q, seen in three tumors, and complete loss of chromosome 14 in one tumor. All three Wilms tumors with unfavorable histology had abnormalities of 17p, resulting in TP53 gene deletion. These findings provide further support for the importance of gains of chromosomes 12, 8, and 6 and loss of 1p in the development of Wilms tumor. The results also support the association of unfavorable-histology Wilms tumors with TP53 deletion. The nonrandom losses of 16/16q, 7p, and 14q may point to the importance of genomic imbalance in the pathogenetic consequences and progression of Wilms tumor.     

Cytogenetic studies on 19 papillary thyroid carcinomas.

Short-term cultures from 19 papillary thyroid adenocarcinomas revealed clonal numerical and/or structural chromosomal changes in 13 tumors, nonclonal abnormalities in one tumor, and only normal karyotypes in five tumors. Clonal abnormalities of chromosome 10 were present in three tumors, two of which had the translocation t(7;10)(q35;q21). Numerical abnormalities of chromosome 17 were detected in two tumors.     

Genomic aberrations in pediatric gliomas and embryonal tumors

The pathogenesis of pediatric central nervous system tumors is poorly understood. To increase knowledge about the genetic mechanisms underlying these tumors, we performed genome-wide screening of 17 pediatric gliomas and embryonal tumors combining G-band karyotyping and array comparative genomic hybridization (aCGH). G-banding revealed abnormal karyotypes in 56% of tumor samples (9 of 16; one failed in culture), whereas aCGH found copy number aberrations in all 13 tumors examined. Pilocytic astrocytomas (n = 3) showed normal karyotypes or nonrecurrent translocations by karyotyping but the well-established recurrent gain of 7q34 and 19p13.3 by aCGH. Our series included one anaplastic oligoastrocytoma, a tumor type not previously characterized genomically in children, and one anaplastic neuroepithelial tumor (probably an oligoastrocytoma); both showed loss of chromosome 14 by G-banding and structural aberrations of 6q and loss of 14q, 17p, and 22q by aCGH. Three of five supratentorial primitive neuroectodermal tumors showed aberrant karyotypes: two were near-diploid with mainly structural changes and one was near-triploid with several trisomies. aCGH confirmed these findings and revealed additional recurrent gains of 1q21-44 and losses of 3p21, 3q26, and 8p23. We describe cytogenetically for the first time a cribriform neuroepithelial tumor, a recently identified variant of atypical teratoid/rhabdoid tumor with a favorable prognosis, which showed loss of 1p33, 4q13.2, 10p12.31, 10q11.22, and 22q by aCGH. This study indicates the existence of distinct cytogenetic patterns in pediatric gliomas and embryonal tumors; however, further studies of these rare tumors using a multimodal approach are required before their true genomic aberration pattern can be finally established.     

Multicolor fluorescence in situ hybridization (SKY) in mycosis fungoides and Sézary syndrome: search for recurrent chromosome abnormalities

Cutaneous T-cell lymphoma (CTCL) is a clonally derived lymphoproliferative disorder that preferentially involves the skin. The two major clinical expressions of CTCL, mycosis fungoides (MF) and Sézary syndrome (SS), have poorly understood pathogenesis. Chromosome abnormalities, mostly complex karyotypes, are seen in about 50% of patients with MF/SS, and there have only been a few instances of recurrent rearrangements. We analyzed 19 blood samples from patients with MF/SS with cytogenetics and multicolor FISH (SKY) to better describe the complex karyotypes and search for recurrent abnormalities or breakpoints. Comparison of phytohemagglutinin (PHA)-stimulated cultures versus a combination of interleukin 2 plus interleukin 7 showed similar efficiency in detecting abnormal clones; however, the PHA cultures yielded more analyzable metaphases. Nine of 19 patients (47%) had an abnormal karyotype. The most frequent abnormalities, in 7 of 9 cases, involved chromosome 10; followed by chromosome 6, in 6 of 9 cases; chromosomes 3, 7, 9, 17, and 19, in 5 of 9 cases; chromosomes 1 and 12, in 4 of 9 cases; and chromosomes 8, 11, and 13, in 3 of 9 cases. Most abnormalities were structural. Recurrent rearrangements included deleted chromosomes 6 and 13, in three cases each, and recurrent breakpoints at 1p32-36, 6q22-25, 17p11.2-13, 10q23-26, and 19p13.3, occurring in three or more cases. One patient had a pseudodicentric translocation between the short arms of chromosomes 8 and 17, confirmed by dual-color FISH and interpreted as psu dic(17;8)(p11.2;p11.2). Two patients with SS reported in the literature seem to have a similar translocation. If confirmed, a psu dic(17;8) could be the first recurring translocation detected in at least three patients with MF/SS.     

Translocation (11;14)(q13;q32) and preferential involvement of chromosomes 1, 2, 9, 13, and 17 in mantle cell lymphoma.

We have studied 13 cases of histologically confirmed mantle cell lymphomas (MCL) combining cytological-immunological features with conventional cytogenetics and in situ hybridization (ISH) techniques. Peripheral blood smears and lymph node biopsies expressed the typical mantle zone pattern with alpha B-cell phenotype. Most of the cases (11 of 13) had lymphomatous cells in the peripheral blood. Chromosome analysis was carried out on lymphoid cells from peripheral blood and/or lymph node biopsies. Phytohemagglutinin (PHA) and phorbol 12-myristate 13 acetate (TPA) were used as mitogens. Biotin-labeled libraries of whole chromosomes implicated in complex karyotypes were used to improve their interpretation. Clonal chromosome abnormalities were found in 10 of 13 patients (77%); 7 of these had a complex abnormality. The most frequent recurrent structural abnormalities were: t(11;14)(q13;q32), involvement of chromosome 1 (der[1], del[1], dup[1]), chromosome 2 (del[2], der[2]), chromosome 9 (der[9], -9), chromosome 13 (add[13], t[13q]), and chromosome 17 (add[17], der[17], t[17q]). The most frequent numerical abnormalities were monosomy 21 and loss of the Y chromosome.     

Chromosomal abnormalities in leiomyosarcomas.

Thirty-eight tumors from 30 patients diagnosed as leiomyosarcoma were cytogenetically assessed after short term culture. The specimens were obtained from the retroperitoneum, gastrointestinal tract, and extremities. Chromosomal abnormalities were present in 18 tumors from 13 patients; 15 tumors had clonal changes, whereas 3 tumors had numerous nonclonal changes. Ten tumors from 10 patients had normal karyotypes and no results were obtained in 10 other tumors from 7 patients. Of the tumors with clonal chromosomal aberrations, 4 had near-diploid (3 hypo- and one hyperdiploid) modes, 8 were polyploid, and 3 were bimodal. No specific karyotypic change appeared to characterize the leiomyosarcomas, although involvement of some chromosomes appeared more frequent than others. A comparison of our findings with those reported in the literature revealed certain consistent structural rearrangements involving chromosomes 1, 7, 10, 13, and 14 at bands 1p36, 1p32, 1p13, 1q32, 7p11.1-p21, 7q32, 10q22, 13q14, and 14p11, respectively. Other bands less frequently rearranged were 3p13-p22, 3q21, 4q13-q23, 6q15-q21, 7q11.2-q22, 12q13-q14, 17q12-q25, 19q13.3-q13.4, and 20q12-q13.1. Numerical changes included recurrent loss of chromosomes 4, 9, 14, 15, 16, 18, 21, and 22. Identification of the abnormalities of these chromosomes is important in that it may predict the existence of oncogenes, tumor suppressor genes, and/or growth factor genes at these sites. Subsequent molecular analysis might then lead to the identification of the genes involved and ultimately to a better understanding of the pathogenesis of leiomyosarcomas.     

Cytogenetics of non-small cell lung cancer: analysis of consistent non-random abnormalities

Cytogenetic analysis of ten primary non-small cell lung carcinomas (NSCLC), including five adenocarcinomas (ADC), three squamous cell (SQC), and two large cell (LCC) carcinomas has been carried out in an attempt to determine karyotype changes involved in the early stage of disease. The tumors were all aneuploid and exhibited complex karyotypes with multiple structural and numerical abnormalities. Clonal structural rearrangements were identified and in particular loss of material from the short arm of chromosome 9 had a 90% incidence. This loss was due to non-reciprocal translocation, deletion, or chromosome loss. Breakpoints were in the region 9q13 to p22. Other chromosome regions that were non-randomly involved are as follows: I cen to p13, 3p, 5q11 to q13, 6p, 6q15 to q27, 7p, 8p, 11q12 to q23, 13p, 14p, 15p, 17p, and 19p. While a primary cytogenetic change in NSCLC has not been identified conclusively, our findings implicate loss of material from 9p as a potentially important event.     

Cytogenetic aberrations in 188 benign and borderline adipose tissue tumors

Chromosome studies of lipomas have revealed an extensive cytogenetic heterogeneity. To investigate the frequencies of previously recognized cytogenetic subgroups and to find out if more recurrent rearrangements can be identified, we have analyzed cytogenetically short-term tissue cultures of 237 samples from 188 adipose tissue tumors obtained from 142 patients. Only one of 58 tumors from 18 patients with multiple lipomas (more than two tumors) had karyotypic changes. Among the sporadic lipomas, 20 tumors had supernumerary ring chromosomes of unknown origin, 55 had different aberrations involving chromosome segment 12q13-15, 11 had changes of 6p or chromosome 13, but no rings or 12q13-15 changes, and 14 had various other aberrations. Ring chromosomes were found in all cytogenetically abnormal lipomas histologically classified as atypical and in nine tumors classified as typical lipoma or spindle cell lipoma. Recombinations between 12q 13-15 and a few other bands or segments were seen more than once: 3q27-28 (15 tumors), 2p22-24 and 2q35 (four tumors), 1 p32-34 and 13q 12-14 (three tumors), and 5q33 (two tumors). Recombinations of 12q 13-15 with 2q35 and 13q 12-14 have not been described before. Of eight tumors with chromosome 13 aberrations, five had loss of 13q material. Aberrations of 12q 13-15, 6p, and/or chromosome 13 were found simultaneously in nine tumors. Two to four samples from the same tumor were investigated in 29 tumors with clonal aberrations. Thirteen of these tumors displayed clonal evolution, also noted in another 17 tumors in which only one sample had been investigated. Thus clonal evolution occurred in 30% of the tumors and was particularly frequent in atypical lipomas. Genes Chrom Cancer 9:207-215 (1994). © 1994 Wiley-Liss, Inc.     

Comparative genomic hybridization detects specific cytogenetic abnormalities in pediatric ependymomas and choroid plexus papillomas

Pathogenesis and genetic abnormalities of ependymomas are not well known and differential diagnosis with choroid plexus tumors may be difficult when these tumors are located in the ventricles. We analyzed 16 samples of primary pediatric ependymomas and seven choroid plexus tumors for significant gains or losses of genomic DNA, using comparative genomic hybridization (CGH). Four ependymoma samples were obtained after surgery for relapse, including one patient whose tumor was analyzed at diagnosis and at first and second relapses. Three out of 16 ependymomas and none of the choroid plexus tumors appeared normal by CGH. In the remaining ependymomas, the number of regions with genomic imbalance was limited. The most frequent copy number abnormality in ependymomas was 22q loss. In one patient from whom multiple samples could be analyzed during tumor progression, no abnormality was present at diagnosis; gain of chromosome 9 and loss of 6q were observed at first relapse and, at second relapse, additional genomic imbalances were loss of 3p, 10q, and chromosome 15. In choroid plexus tumors, recurrent abnormalities were gains of chromosome 7 and region 12q. The recurrent chromosomal abnormalities were clearly different between ependymomas and choroid plexus papillomas (CPP). Recurrent loss of 22q suggests that this region harbors tumor suppressor genes important in the pathogenesis of ependymomas; however, other pathogenic pathways may exist involving 6q and chromosome 10 losses or gain of 1q and chromosome 9. CPP can be distinguished from ependymoma on the basis of CGH abnormalities.     

Nonrandom karyotypic features in basal cell carcinomas of the skin.

Cytogenetic analysis of short-term cultured 44 basal cell carcinomas (BCC) revealed clonal karyotypic abnormalities in 38 tumors. Relatively complex karyotypes (at least four structural and/or numerical changes per clone) with unbalanced structural as well as numerical aberrations were found in eight (approximately 21%) of the BCC, while the remaining BCC (79%) had simple karyotypes (1 to 3 aberrations per clone). Numerical changes only were found in 16 tumors, 15 BCC displayed both numerical and structural aberrations, and the remaining 7 BCC showed only structural aberrations. Extensive intratumoral heterogeneity, in the form of cytogenetically unrelated clones, was found in 21 tumors, whereas related subclones were present in 10 tumors. In order to obtain an overall karyotypic picture in BCC, the findings of our previously published 25 BCC have been reviewed. Our combined data indicate that BCC are characterized by nonrandom karyotypic patterns. A large subset of BCC is characterized by nonrandom numerical changes, notably, +18, +X, +7, and +9. Structural rearrangements often affect chromosomes 1, 4, 2, 3, 9, 7, 16, and 17. A number of chromosomal bands are frequently involved, including 9q22, 1p32, 1p22, 1q11, 1q21, 2q11, 4q21, 4q31, 1p36, 2q37, 3q13, 7q11, 11p15, 16p13, 16q24, 17q21, and 20q13. When the genomic imbalance is assessed, it has been shown that several chromosome segments are repeatedly involved in losses, namely loss of the distal part of 6q, 13q, 4q, 1q, 8q, and 9p. A correlation analysis between the karyotypic patterns and the clinico-histopathologic parameters has been undertaken in the 44 BCC of the present series. The cytogenetic patterns show a significant correlation with tumor status (P=.025), that is, that cytogenetically more complex tumors are also those clinically the most aggressive. Also, the frequency of cytogenetically unrelated clones is significantly higher in recurrent BCC than that in primary lesions (P=.05). No clear-cut association has been found between the karyotypic patterns and histologic subtypes or tumor sites.     

Non-random chromosome rearrangements in adenoid cystic carcinoma of the salivary glands

The chromosomal findings in 10 adenoid cystic carcinomas (ACC) of the salivary glands are described. Clonal numerical deviations as the sole anomaly were detected in four cases and structurally rearranged stemlines and sidelines in four cases. An apparently identical t(6;9)(q23;p21) was found in two tumors; in one case the translocation was part of the abnormal stemline and in the other case it was the sole anomaly in a single variant cell. A similar or identical t(6;9)(q21-24;p13-23) has recently been reported in three of 15 previously published cases of ACC. The three remaining tumors with abnormal stemlines all had rearrangements of chromosome 9, including t(1;9)(q21;p21-22), der(9)i(9)(q10)inv(9)(q12q 13), and der(X)t(X;9)(p21;p22-23), respectively. The latter case also had a t(17;18)(p12;q11.2) that was common to both abnormal clones present in this tumor. In addition to other abnormalities, the clone with der(X)t(X;9) also showed a del(6)(q13q21). In two cases fluorescence in situ hybridization (FISH) was used for further characterization of the marker chromosomes. A survey of the present findings together with previous results from 15 ACC clearly demonstrates that rearrangements of 6q21-24 (deletions or translocations in 11 cases), 9p13-23 (translocations in seven cases), and 17p12-13 (translocations in three cases) are recurrent, and often primary, in ACC, and that the t(6;9)(q21-24;p13-23), found in five tumors, is a non-random, primary aberration. Genes Chromosom Cancer 10:115–121 (1994). © 1994 Wiley-Liss, Inc.