Alterations affecting chromosome 1 are among the most common abnormalities in solid tumors as well as hematological malignancies. These abnormalities include translocations and other structural rearrangements involving chromosome 1 and various other chromosomes, as well as deletions or amplifications affecting whole chromosome arms or specific regions. This section of the workshop report contains a summary of data on chromosome 1 involvement in cancer published from September 1999 through October 2000. In addition, data presented at this workshop are discussed in more detail.

CGH based studies

Comparative genomic hybridization (CGH) analyses have been used by numerous research groups throughout the world as a method for analyzing copy number changes in tumors. This section summarizes data published during the last year. Previous CGH analyses may have revealed recurrent gains or losses involving chromosome 1 material also in cancers not mentioned here. As reported previously, losses seem to most frequently include the short arm (1p) of the chromosome whereas gains are more often associated with the long arm (1q).

Loss of 1p was detected in 42% of breast cancer cell lines (Forozan et al., 2000); in endometrial hyperplasia, especially in complex hyperplasia (Kiechle et al., 2000); and in primary and metastatic gastrointestinal tumors (51%) (El-Rifai et al., 2000b).

Local losses were assigned to 1p21-p22 in 41% of parathyroid carcinomas (Kytola et al., 2000), to 1p11-p32 and 1cen-p31 in pheochromocytomas and abdominal paragangliomas (in 86% and 82%, respectively), and loss of 1p material was suggested to be an early event (Dannenberg et al., 2000; Edstrom et al., 2000). Uterine leiomyomas and leiomyosarcomas displayed both gains and losses affecting 1p (Levy et al., 2000), as did anaplastic thyroid carcinomas, which also showed gain and loss of 1q (Wilkens et al., 2000).

Gain of 1p was detected in non-small lung carcinomas and neuroendocrine carcinomas (Michelland et al., 1999) and in breast cancer (Loveday et al., 2000), and high-level amplification of 1p13 was observed in 11% of breast cancer cell lines (Forozan et al., 2000). Studies of a panel of malignant ovarian germ cell tumors revealed gains of 1p in 33% of dysgerminomas and 2/9 immature teratomas, and gain of 1q in 3/4 endodermal sinus tumors (Kraggerud et al., 2000). Perlman and colleagues (Perlman et al., 2000) detected gain of 1q in 6/16 and loss of 1p in 4/16 childhood endodermal sinus tumors. Loss of 1q42-qter was observed in 9/45 leiomyosarcomas, loss of 1p36 in 8/45 cases, and gain of 1q12-q31 in 6/45 cases (Mandahl et al., 2000). Loss of 1p was more frequent in metastatic leiomyosarcomas. Loss of 1p and gain of 1q occurred with similar frequencies in hepatocellular carcinomas (HCC) associated with hepatitis B or C infection as in non-infected patients (Marchio et al., 2000), affecting 35% and 46% of the cases, respectively (Sakakura et al., 1999; Guan et al., 2000; Zondervan et al., 2000). In separate studies, gain of 1q was also found in non-infected HCC (Marchio et al., 2000) and in 66% of HCC (Guan et al., 2000). In squamous cell carcinomas of the oropharnyx and hypopharynx, gain of 1p was detected exclusively in nonmetastasing tumors (4/20), with gains of 1q observed only in metastatic tumors (Welkoborsky et al., 2000).

Gain of 1q was among the most consistent aberrations found in invasive breast carcinomas and was more frequent in high-grade ductal breast carcinomas with overexpression of c-erbB-2 and estrogen receptor positivity (Malamou-Mitsi et al., 1999). Gains of 1q were found also in lobular, ductal and invasive ductal in situ carcinoma of the breast, in lymph node metastases (Aubele et al., 2000a; Buerger et al., 2000; Vos et al., 1999), and in 61% of breast cancer cell lines (Forozan et al., 2000; Kytola et al, 2000). Gain of 1q was also reported in 26% (Weber et al., 2000b) and 32% (Rickert et al., 1999) of diffuse large B-cell lymphomas of the central nervous system, cervical carcinomas (Matthews et al., 2000), endometrial cancers (but not in precursor lesions) (Kiechle et al., 2000), esophageal squamous cell carcinomas (Mayama et al., 2000), 41% of hepatoblastomas (Weber et al., 2000a), 6/10 cases of nasopharyngeal carcinoma (Fan et al., 2000), 16% of prostate cancer, 50% of retinoblastomas (Mairal et al., 2000), 54% of renal cell carcinoma cell lines (Yang et al., 2000) and schistosoma as well as non-schistoma-related bladder cancers (El-Rifai et al., 2000a; Muscheck et al., 2000).

Gains of 1q in squamous cell carcinomas of the head and neck were more frequent in aggressive metastatic tumors (Bergamo et al., 2000) and were the most frequent aberration in well differentiated thymic carcinomas (B3 thyomas, 69%), and the second most common (56%) aberration in primary thymic squamous cell carcinomas (Zettl et al., 2000).

Surprisingly, gains of 1q were not detected in Spitz nevi, which are benign neoplasms of melanocytes, although they were reported to occur in 25% of their malignant counterpart, primary cutaneous melanoma (Bastian et al., 1999).

Local gains or high-level amplifications affecting 1q were reported for the following tumors: breast cancer cell lines (89%, 1q21-q32) (Larramendy et al., 2000) hepatocellular carcinomas (1q12-q22) (Guan et al., 2000), schistoma as well as non-schistoma related bladder cancer (El-Rifai et al., 2000a), intratubular germ cell neoplasia and invasive components of non-seminoma (Looijenga et al., 2000), pancreatic acinar carcinomas (1q21 in 4/6 and 1q42 in 3/6) (Taruscio et al., 2000), and retinoblastoma (1q21) (Mairal et al., 2000). Tarkkanen and coworkers (Tarkkanen et al., 1999) analyzed pairs of primary sarcomas and their pulmonary metastases and found that amplifications affecting 1q (1q21-q23) occurred in 36% of the primary tumors and 45% (1q21) of the metastases. In parathyroid carcinomas, local gains were assigned to 1q23-q31 and occurred earlier than loss of 1p, but both aberrations were significantly more common in carcinomas than in adenomas (Kytola et al., 2000).

Brain tumors

Meningiomas are the most common brain tumors in adults. It is a recurrent, but relatively benign, tumor that is about two times more frequent in women. LOH at 1p occurs in about 35% of the cases, and is thus the second most common aberration. Based on LOH analyses of a large panel of tumors, Sulman and collaborators (this workshop) identified a smallest region of overlap spanning 1.5 cM, between the markers D1S596 and D1S2852. Of the samples analyzed, 34% showed LOH at this site. Furthermore, LOH at 1p was associated with advanced grade tumors (III), was predictive of tumor recurrence, and correlated with loss of chromosome 22 and mutation of NF2. Bello and coworkers (Bello et al., 2000a) also reported allelic loss at 1p in meningiomas. The patterns of loss indicated two main target regions, 1p36 and 1p32-p34, whereas losses at 1p22 and 1p13-p21 were less common. Also Santarius and coworkers (Santarius et al., 2000) detected LOH in 1p32, near the markers D1S193 (37% + one homozygous deletion), D1S463 (20%) and D1S211 (25%). The CDKN2C/p18(INK4C) gene was screened for mutations and inactivating methylation in these samples, but no aberrations were detected. Karyotype analyses of meningiomas revealed loss of 1p in 18% of the tumors, caused by a translocation involving 1q10. In two tumors, a novel whole arm translocation der(1;2)(q10;q10) was observed (Sawyer et al., 2000b).

Deletions of D1Z1 and D1Z2 at 1p36 were observed in 27% of common type meningiomas, 70% of intermediate type and 100% of anaplastic meningiomas. Monosomy of 1p was strongly associated with loss of alkaline phosphatase (ALPL) activity (Muller et al., 1999). Lamszus and colleagues (Lamszus et al., 2000) have analyzed a panel of neurofibromatosis 2 (NF2)-associated meningiomas. Next to LOH flanking the NF2 locus, LOH of 1p was the second most common region of loss (40%). Loss of 1p was found also in radiation induced meningiomas (RIM) (4/7), but in contrast to the sporadic cases, RIM tumors had no mutations in NF2 (Shoshan et al., 2000). Furthermore, a novel unbalanced translocation, der(1)t(1;3)(p12-p13, q11) was reported for three cases of chordoid meningiomas (Steilen-Gimbel et al., 1999).

LOH at 1p36 and 19q occur in 80-90% of oligodendrogliomas, but occur at lower frequencies in other gliomas, such as anaplastic astrocytomas and glioblastomas. This LOH is of clinical importance in oligodendrogliomas with LOH at 1p/1p36 and 19q, as these aberrations are predictors of overall longer survival. However, this association was not evident in patients with astrocytomas or mixed oligoastrocytomas (Smith et al., 2000). Bello and colleagues (Bello et al., 2000b) observed deletions in chromosome 1 in 26 tumors from a series of 35 oligodendrogliomas, mostly on the short arm. They also screened the hRAD54 gene from the 1p32 region for mutations in 25 tumors, but no etiologic changes were found. McDonald and coworkers (this workshop) described an array-based strategy for identification of genetic markers in 1p36 that can be helpful in sub-classification of gliomas, and in particular, to predict chemotherapy response in these tumors.

Gliomas of astrocytic and mixed astrocytic-oligodendroglial phenotypes also show 1p loss (9/9 cases). A larger panel of high-grade astrocytoma was also examined, and loss of 1p was detected in 10% of the samples (Ino et al., 2000). LOH of 1p occurred at a similar frequency in primary and secondary glioblastomas (12 and 15%, respectively) (Nakamura et al., 2000).

Breast cancer

Tsarouha and collaborators (Tsarouha et al., 1999) studied the clonal evolution in breast carcinomas carrying an i(1q) or a der (1;16)(q10;p10) as the primary chromosomal abnormality. There was a difference between the two in that tumors with i(1q) showed frequent occurrence of +20 which was found mainly in younger patients, whereas +7 was associated with der (1;16)(q10;p10) and shorter survival.

Loveday and colleagues (Loveday et al., 2000) reported a correlation between 1q gain and the absence of telomerase expression in breast cancer, indicating that genes located in 1q may be involved in telomerase expression.

Aubele and coworkers (Aubele et al., 2000b) analyzed lumpectomy specimens from patients with different stages of ductal breast carcinoma, ranging from hyperplasia without atypia to invasive carcinomas. They reported that the number of chromosomal changes increases with increasing histological severity, and gain of 1q was identified in both ductal carcinoma in situ and in the invasive cancers. Extra 1q material may be present in breast cancer in the form of ring chromosomes (Adeyinka et al., 2000).

LOH at 1p was found in association with loss of 8p in some cases of sporadic breast cancers as well as some tumors from patients carrying the BRCA 2999del5 mutation. LOH of 8p occurs in 50% and 78% of these patient groups, respectively (Sigbjornsdottir et al., 2000). Furthermore, LOH at 1p was detected in 16% of bilateral breast cancer (Imyanitov et al., 2000) and was more frequent in ductal than in lobular breast carcinomas (Huiping et al., 1999).

Colon cancer

Patients with hyperplastic polyposis have an increased risk for developing colon cancer. Rashid and coworkers (Rashid et al., 2000) examined hyperplastic polyps (HP) from 13 patients and found that the presence of HP was associated with loss of 1p in 21% of the cases. Their results indicated that patients with HPs showing loss of 1p were more prone to develop hyperplastic dysplasia and adenocarcinoma.

Chadwick and colleagues (Chadwick et al., 2000) found mutations of the RIZ gene in 37.5% of primary colorectal cancers and 54% of the cell lines examined. The mutations were 1 or 2 bp deletions of a coding A (8) or C (9) tract and were confined to tumors with microsatellite instability. Reduced or absent expression of RIZ1 was observed in 4/11 cell lines, and in one cell line, a truncated RIZ protein was found. RIZ was proposed as the target gene for the observed 1p deletion in these cancers. Allelic loss affecting 1p33-p35 and 1p36 was not detected in a large panel of early colorectal adenomas from familial adenomatous polyposis (FAP) patients (Lamlum et al., 2000).

Leukemia

Jumping translocations (JT) involving 1q23 were reported for two cases of acute lymphoblastic leukemia. The translocations resulted in trisomy for (1)(q23->qter), and both patients died within 2 years after the appearance of the JT (Jarvis et al., 1999).

Pedersen and collaborators (Pedersen et al., 2000) examined unbalanced translocations in a large panel of myeloid hemopoietic malignancies and found trisomy of 1q in 25/49 cases, mainly in younger patients. Sixteen of these cases had the translocation t(1;7)(q10, p10), resulting in trisomy of 1q and monosomy of 7q. These patients also exhibited a shorter survival.

A large series of samples from patients with myelodysplastic syndrome have been examined to identify single chromosomal abnormalities associated with prognosis. Patients with single 1q abnormalities experienced poor survival in univariate analyses (Sole et al., 2000).

Dicentric chromosomes are often observed in myelodysplasia and acute myeloid leukemia. Andersen and coworkers (Andersen and Pedersen-Bjergaard, 2000) found that this phenomenon was more frequent in therapy-related forms of the diseases than in de novo diseases (27/180 versus 7/231). In 10 of the 27 cases with dicentric chromosomes, a dic(1q;7) was observed, frequently resulting in trisomy of 1q. Moreover, the presence of dicentric chromosomes was significantly associated with previous therapy using alkylating agents.

Liver cancer

Two cases of hepatoblastoma (HBT) have been reported in which complex numerical abnormalities involved multiple regions of 1q, resulting in partial 1q tetrasomy for one of the cases (Nagata et al., 1999), In a more recent report, the 1q rearrangements of HBT have been studied in more detail. Three of the seven cases examined had translocations involving 1q12-q21 [t(1;2), t(1;4) and t(1;11)], resulting in gain of 1q material, and FISH analysis revealed that all the breaks occurred in the heterochromatin region (Parada et al., 2000). Curiously, rat hepatocellular carcinomas also showed elevated allelic imbalances affecting 1q among other chromosomal abnormalities, but overall, LOH and allelic imbalances seemed to play a less significant role in these tumors than in their human counterparts (Teeguarden et al., 2000).

It was recently shown that hepatocellular chirrotic nodules with allelic loss at 1p, 4q, 13q and 18q are more prone to develop hepatocellular carcinoma (Roncalli et al., 2000).

Lung cancer

Girard and colleagues (Girard et al., 2000) studied LOH on a genome-wide scale in small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) and found a similar frequency of LOH in the two subtypes. LOH affecting 1p was among the most frequent findings.

Frequent allelic imbalances have been noted at the TP73 locus in 1p36, although no mutations have been reported. Detailed deletion mapping revealed losses of 1p36 in 50% of the cases examined, most frequently affecting the marker D1S508 (45%). Several cases showed loss of a subtelomeric region distal to D1S2845 in 1p36.3, whereas loss of 1p32-p34 was less frequent (11%) (Nomoto et al., 2000).

Lymphoid tumors

Translocations or duplications affecting 1q21 are frequently observed in various subgroups of lymphomas. Dyomin and coworkers (this workshop) reported the mapping and cloning of two different breakpoints in two cases of diffuse large B-cell lymphomas (DLBL) with t(1;14)(q21;q32). In one of the cases, the MUC1 gene was fused to IGH, leading to activation of MUC1 by the IGH enhancer. The other breakpoint in 1q21 mapped in the FCg cluster region, resulting in activation of an aberrant isoform of FCGIIB. Analyses of larger panels of DLBL showed that the breakpoints were recurrent.

Callanan and collaborators (this workshop) analyzed non-Hodgkin's lymphomas (NHL) patients and B-cell tumor lines and reported three novel breakpoint sites. One occurred in the heterochromatin band 1q12 and was frequent both in follicular lymphomas and DLBL, accounting for 40% of the breaks observed. The two remaining sites were located within 2.5 Mb of proximal 1q21, with one region occurring most frequently in high grade lymphomas and spanning markers D1S3620 to WI-5662, and the other region spanning markers WI-5663 to D1S3623 and occurring more frequently in the low grade lymphomas. Of the possible candidate gene from this region, AF1 showed rearrangement in one tumor, but BCL9 was not affected.

REAL classification of peripheral T-cell lymphoma showed that structural rearrangements involving 1p or 1q were found in 17.5 and 22.8% of the cases, respectively (Lepretre et al., 2000).

Melanoma

Chromosome 1 abnormalities are also frequent in malignant melanomas, and specific breakpoints are associated especially with 1p36 and 1p22-q21. In a study of seven melanoma cell lines, deletions involving 1p32-10, 1q11-q44 and 1q25-q44 were observed. Three breakpoints were mapped to 1q10-q11, with additional breakpoints identified in 1p36, 1p32, 1p31, 1p12-p13, 1q21 and 1q23 (Smedley et al., 2000).

Deletions of 1p36.3 were found in seven melanoma cell lines, 91% of metastatic samples and 63% of nodular melanomas analyzed, and were confined to a locus near D1Z2 (Poetsch et al., 1999).

Neuroblastoma (NB) and neurocytoma

Taylor et al reported that MYCN amplification, 1p deletion and aneuploidy were the most powerful for prediction of prognosis in NB (Taylor et al., 2000).

Ohira and collaborators (Ohira et al., 2000 and this workshop) identified a homozygously deleted region of approximately 500 kb near the marker D1S244 in 1p36.2-p36.3. The deletion was found in two NB cell lines but could not be detected in 188 patient tumor samples. However, four of the six suggested candidate genes, RERE/DNB1/ARPh, KIF1B, PEX14 and DFFA, showed lower expression levels in NB patients with an unfavorable outcome. Another possible candidate in this region, KIAA0591, was expressed in favorable NB but not in unfavorable ones, but no mutations were detected in the coding region of this gene (Nagai et al., 2000).

Spieker and coworkers (Spieker et al., 2000) suggested that 1p36 deletions affect different loci in MYCN single-copy NB and MYCN amplified NB. The first deletions affect a 20 cM region in 1p36.3, while the second was mapped between 56.6 and 57.2 cM from 1ptel. The 5 Mb region was mapped in more detail, and several genes associated with cell growth, differentiation and morphogenesis are located there.

Abel and Martinsson (this workshop) screened primary NB samples for mutations in Caspase-9, a key player in the apoptotic pathway. No mutations could be found, but CASP9 and the isoform CASP9S were expressed in all stages of NB, but showed lower expression in stage 3 and 4 tumors. Amler and colleagues (Amler et al., 2000) cloned two possible target genes from 1p36.1-p36.2. RERE/DNB1/ARPh is highly related to the DRPLA gene and is ubiquitously expressed in adult and fetal tissue. The second gene, DNB5, is predominantly expressed in brain tissue and fetal kidney, and shows no homology to any known genes. Both genes are expressed in NB cell lines.

Also, 1p32-p34 is commonly deleted in high grade NB, but the Patched-2 gene was not deleted. Four of the 14 cases showed sequence variations leading to amino acid substitutions, but these variations were also found in normal DNA from the same patients (Jogi et al., 2000).

Neurocytomas are rare tumors of the central nervous system. Tong and coworkers (Tong et al., 2000) examined a panel of these tumors and their matched blood samples for LOH affecting 1p and found LOH in 5/9 tumors, but they could not identify a common region of loss.

Thyroid cancers

Parathyroid adenomas (PTA) are particularly frequent in elderly females and may affect up to 2.1% of women in this group. Mutations in the MEN1 gene were found in 12-15% and 18% show amplification of CCDN1, but allelic loss at 1p was reported as the most frequent genetic alteration in these tumors. The deletions were mapped close to D1S228 in 1p36. Carling and colleagues (this workshop) described LOH analyses of 1p with a panel of PTA tumors and found LOH of D1S214 in 23.7% and LOH of RIZ in 28.6% of the cases. In four of the tumors, LOH at Pro704 of RIZ was the only deletion found. LOH at RIZ/Pro704 was also detected in 42% of pheochromocytomas, and in several of these, RIZ alone showed LOH. LOH of D1S228 was detected in 44% of these tumors. These results suggest that RIZ is located in the minimal deleted region of thyroid cancers, but it is not known whether the remaining allele of RIZ is inactivated. RAD54, another candidate gene for deletions in PTA located in 1p32, was examined for mutations, but none were found (Carling et al., 1999).

Dwight and collaborators (Dwight et al., 2000) analyzed a large panel of parathyroid tumors and their matched blood samples for LOH affecting 1p and 1q. LOH at 1p was detected in 18% of the cases, whereas 9% of tumors exhibited loss of 1q21-q32, always in association with LOH at 1p.

Papillary thyroid cancer (PTC) is usually sporadic, but first degree relatives of PTC patients seem to have a higher incidence of PTC, thus indicating an inheritable form of the disease. Malchoff and colleagues (this workshop) identified linkage of familial PTC to a 22 cM region between the markers D1S3009 and D1S2721 in 1q21-q22. There are several possible candidate genes in this region, but those tested so far&endash;NRAS, NTRK and PRCC&endash;were excluded.

Another group (Kitamura et al., 2000b) reported allelic imbalances affecting 1q to be the most frequent (37%) in aggressive PTC tumors. The same group also studied allelic imbalances in anaplastic thyroid carcinomas (APC) and found loss at 1q in 40% of the cases. The deleted region was defined within 1q31-q42 (Kitamura et al., 2000a).

Haven and coworkers (Haven et al., 2000) reported linkage of the hyperparathyroidism-jaw tumor syndrome (HPT-JT), which is associated with ossifying fibroma of the jaw and various renal lesions, to a 14 cM region spanning the markers D1S413 and D1S477 in 1q25-q31. Carpten and colleagues (Carpten et al., 2000 and this workshop) mapped a hereditary prostate cancer (HPT) locus to the same region and described a strategy for identification of candidate target genes for both HPT and HPT-JT.

Sarcomas

Amplifications affecting 1q21-q22 were found in a variety of tumors, with frequencies varying from 10-20% up to 70% among the different tumor types. In sarcomas, which are malignant tumors of mesenchymal origin, amplification of this region is frequent and more localized than in other tumor types. Forus and coworkers (this workshop) reported the cloning and characterization of three novel candidate genes from the most amplified portion of 1q21, near D1S3620, called COAS1, 2 and 3 (for Chromosome One Amplified Sequence). COAS1 encodes a mRNA of more than 10 kb and shows no sequence homology to any known genes. COAS2 is a member of a protein family that may be involved in stress response, chemotherapy resistance and differentiation of muscle, fat and bone. COAS3 shows sequence homology to the profilin family of actin binding proteins. The three genes were expressed in most normal tissues and showed amplification as well as elevated expression levels in sarcoma samples. COAS1 and COAS2 were more frequently amplified than COAS3.

Stock and colleagues (Stock et al., 2000) used CGH to analyze osteosarcomas and found gains at 1p in 8/21 tumors. In contrast to previous reports, these investigators found no correlation between gains of 1q21, which were relatively rare in this material, and unfavorable prognosis.

Other tumors

Isochromosome 1q leading to tetrasomy of 1q was reported as the sole abnormality in two cases of fetal teratoma arising from the oral cavity. In one of the patients, the teratoma had maternal 1q marker alleles that were not found in the fetal body cells, indicating that the chromosomally normal fetus might be a result of a zygote rescue mechanism (Scheres et al., 1999).

Sawyer and coworkers (Sawyer et al., 2000a) reported the presence of allelic imbalances (AI) on 1q in 30% of the phyllodes tumors examined. Phyllodes tumors are fibroepithelial mammary lesions that tend to have a benign behavior but often turn sarcommateous. AI affecting 1q was found both in epithelium and stroma of these tumors.

Using a genome-wide panel of microsatellite markers, loss of heterozygosity was reported at 1p for 37% of nasopharyngeal carcinomas, which is a common cancer in China but not in the rest of the world (Lo et al., 2000).

LOH at 1p has been studied in papillary serous carcinoma of the peritoneum (PSCP) and compared to allelic loss in serous epithelial ovarian carcinomas (SEOC). LOH at 1p/1p36 was significantly lower in PSCP (Huang et al., 2000).

LOH of 1p and 1q was also detected in 48.5% and 40.6% of intrahepatic cholangiocarcinoma, respectively, but were not the most frequently lost regions (Kang et al., 2000).

Steenman and colleagues (Steenman et al., 2000) described two novel translocation breakpoints on 1p occurring in a Beckwith-Wiedemann syndrome-associated Wilms tumor and rhabdomyosarcoma. The two breakpoints are at least 875 kb apart. A PAC was identified that spanned the rhabdomyosarcoma breakpoint that was located proximal to the PAX7 gene.

Mutation of the TP73 gene was detected in 1/15 Merkel cell carcinomas, and polymorphisms were detected in four of these tumors (Van Gele et al., 2000).

LOH of 1p35-p36 was found in 56% of Wilms tumor, with a minimal region of overlap near D1S247 (Steinberg et al., 2000).

Squamous cell carcinomas frequently show overrepresentation of 1q and frequent rearrangements in 1p10-q12. Furthermore, the presence of isochromosomes 1p or 1q are common (Jin et al., 1999).