Three distinct commonly deleted regions of chromosome arm 16q in human primary and metastatic prostate cancers

Human prostate cancers frequently show loss of heterozygosity (LOH) at loci on the long arm of chromosome 16 (16q). In this study, we analyzed prostate cancer specimens from 48 patients (Stage B, 20 cases; Stage C, 10 cases; cancer death, 18 cases) for allelic loss on 16q, using either restriction fragment length polymorphism (RFLP)- or polymerase chain reaction (PCR)-based methods. Allelic losses were observed in 20 (42%) of 48 cases, all of which were informative with at least one locus. Detailed deletion mapping identified three distinct commonly deleted regions on this chromosome arm: q22.1–q22.3, q23.2–q24.1, and q24.3-qter. On the basis of a published sex-averaged framework map, the estimated sizes of the commonly deleted regions were 4.7 (16q22.1–q22.3), 17.2 (16q23.2–q24.1) and 8.4 cM (16q24.3-qter). Allelic losses on 16q were observed more frequently in the cancer-death cases (11 of 18; 61%) than in early-stage tumor cases (9 of 30; 30%; P < 0.05). In 7 of 11 patients from whom DNA was available from metastatic cancers as well as from normal tissues and primary tumors, the primary cancer foci had no detectable abnormality of 16q, but the metastatic tumors showed LOH. These results suggest that inactivation of tumor suppressor genes on 16q plays an important role in the progression of prostate cancer. We also analyzed exons 5–8 of the E-cadherin gene, located at 16q22.1, in tumor DNA by means of PCR-single strand conformation polymorphism and direct sequencing, but we detected no somatic mutations in this candidate gene. Genes Chromosom Cancer 17:225–233 (1996). © 1996 Wiley-Liss, Inc.     

Comparison of alterations of chromosome 17 in carcinoma of the ovary and of the breast

 Breast and ovarian carcinomas share a region of allelic loss on chromosome 17q25, suggesting that these tumours may arise by similar molecular pathways. We analysed paraffin-embedded tissues from 84 sporadic ovarian carcinomas and 42 sporadic infiltrating ductal carcinomas of the breast for abnormalities on chromosome 17. Loss of heterozygosity (LOH) of at least one informative marker on 17q was identified in 49 of 82 (60%) ovarian carcinomas, as against only 6 of 40 (15%) informative breast carcinomas (P<0.0001). In ovarian carcinoma, LOH was most commonly observed for GH on 17q23 (56%), and was also frequently observed at 17q21 (46%). In contrast, LOH of D17S1330/CTT16 on 17q25 was observed in only 19% of ovarian tumours. LOH in breast carcinomas was most frequently observed at 17q21 (16%), less frequently at 17q23 (7%) and not identified at all at 17q25 in any breast cancers. Immunohistochemical analysis demonstrated overexpression of the p53 gene product in 38 of 84 (45%) ovarian carcinomas, as against 10 of 42 (24%) breast carcinomas (P=0.0195). p53 immunoreactivity was significantly associated with LOH in ovarian and breast cancers. Immunohistochemical expression of HER2/neu was observed in 6 of 84 (7%) ovarian and 3 of 42 (7%) breast carcinomas. There was no relationship between HER2/neu immunoreactivity and LOH. Although sporadic carcinomas of breast and ovary share some regions of allelic loss on chromosome 17q, differences in other alterations on this chromosome suggest divergent pathways of tumour development. Received: 8 July 1998 / Accepted: 6 January 1999     

Loss of heterozygosity on chromosome arm 16q in breast cancer metastases

One of the main genetic abnormalities associated with breast carcinogenesis is the loss of genetic material from chromosome arm 16q. Different groups have identified two regions (16q22.1 and 16q24-ter) that are frequently deleted in primary tumors, suggesting the presence of tumor suppressor genes in these regions. Little is known about the late stages of tumor progression in this respect, and we, therefore, analyzed biopsy specimens of breast cancer metastases for deletions in these critical regions of 16q. We examined fine needle cytopunctures from 24 metastases, each with lymphocyte DNA, for allelic imbalance on 16q by means of polymerase chain reaction (PCR) with 15 highly polymorphic markers. All the metastatic samples showed deletion of at least one informative locus on 16q. The loss of heterozygosity (LOH) pattern often indicated the loss of a complete long arm of chromosome 16 (13 cases); nevertheless, in the remaining 11 samples, partial LOH patterns were observed. A small region of overlap (SRO2) in 16q22.1 was frequently involved, whereas another (SRO1) in 16q24-ter was affected in only two cases. A third region of LOH in 16q22.2-q23.2 was found in 6/11 samples. These results suggest that at least three different regions are involved in allelic imbalance on chromosome arm 16q in breast cancer. Loss of material from the third region could be a major event in the genesis of metastases. Genes Chromosom. Cancer 19:185–191, 1997. © 1997 Wiley-Liss Inc.     

Significance of chromosome arm 14q loss in nonpapillary renal cell carcinomas

We examined 88 nonpapillary renal cell carcinomas for allelic loss at chromosome arm 14q and correlated the results to size, grade, and stage of these tumors. Fourteen highly polymorphic microsatellite markers on the long arm of chromosome 14 were used for deletion mapping. Loss of heterozygosity (LOH) at the smallest overlapping segment of 14q24.2-qter was seen in 42 of 88 tumors. There was no significant correlation between frequency of 14q LOH and size of tumors (P = 0.11). LOH was frequently seen in grade 2 and 3 tumors (55% and 73%, respectively) and in stage III and IV tumors (53% and 80%, respectively). We found a significant correlation between chromosome arm 14q LOH and nuclear grade (P < 0.001) and stage (P < 0.001) of tumors. These observations indicate the presence of a tumor-suppressor gene at chromosome segment 14q24.2-qter and demonstrate the usefulness of microsatellite analysis for assessing the possible clinical outcome of nonpapillary renal cell carcinomas. Genes Chromosom. Cancer 19:29–35, 1997. © 1997 Wiley-Liss, Inc.     

Loss of heterozygosity or allele imbalance in histologically normal breast epithelium is distinct from loss of heterozygosity or allele imbalance in co-existing carcinomas

To better understand early steps in human breast carcinogenesis, we examined allele imbalance or loss of heterozygosity (LOH), in co-existing normal-appearing breast epithelium and cancers. We microdissected a total of 173 histologically normal ducts or terminal ductolobular units (TDLUs) and malignant epithelial samples from 18 breast cancer cases, and examined their DNA for LOH at 21 microsatellite markers on 10 chromosome arms. Fourteen of 109 (13%) normal ducts/TDLUs, from 8 of 18 (44%) cases, contained LOH. The location of these 14 ducts/TDLUs appeared unrelated to distance from the cancer. LOH in normal-appearing epithelium involved only single markers, whereas LOH in cancers commonly encompassed all informative markers on a chromosome arm. In only 1 of 14 (7%) ducts/TDLUs with LOH, was the same LOH seen in the co-existing cancer. Global differences in LOH per arm in normal-appearing tissue were not demonstrated, but less LOH was seen at 11q and 17p than at 1q (P = 0.002), 16q (P = 0.01), and possibly 17q (P = 0.06). These results indicate that in a large fraction of women with breast cancer, histologically normal breast epithelium harbors occult aberrant clones. Individual clones rarely are precursors of co-existing cancers. However, they might constitute a reservoir from which proliferative lesions or second cancers develop once additional genetic abnormalities occur, they could contribute to intratumoral genetic heterogeneity, and they are consistent with a role for genetic instability early in tumorigenesis.     

Biallelic inactivating mutations and an occult germline mutation of PTEN in primary cervical carcinomas

A tumor suppressor gene on chromosome sub-band 10q23.3, PTEN, is frequently mutated or deleted in a variety of human cancers. Germline mutations in PTEN, that encodes a dual-specificity phosphatase, have been implicated in two hamartoma-tumor syndromes that exhibit some clinical overlap, Cowden syndrome and Bannayan-Zonana syndrome. Although cervical cancer is not a known component of these two syndromes, loss of heterozygosity (LOH) of markers on chromosome arm 10q is frequently observed in cervical cancers. To determine the potential role that PTEN mutation may play in cervical tumorigenesis, we screened 20 primary cervical cancers for LOH of polymorphic markers within and flanking the PTEN gene, and for intragenic mutations in the entire coding region and exon-intron boundaries of the PTEN gene. LOH was observed in 7 of 19 (36.8%) cases. Further, one sample may have homozygous deletion. Three (15%) intragenic mutations were found: two were somatic missense mutations in exon 5, that encodes the phosphatase motif, and an occult germline intronic sequence variant in intron 7, that we show to be associated with aberrant splicing. All three samples with the mutations also had LOH of the wild-type allele. These data indicate that disruption of PTEN by allelic loss or mutation may contribute to tumorigenesis in cervical cancers. In cervical cancer, unlike some other human primary carcinomas, e.g., those of the breast and thyroid, biallelic structural PTEN defects seem necessary for carcinogenesis. Further, one in 20 unselected cervical carcinomas was found to have a germline PTEN mutation; it is unclear whether the patient with this mutation had Cowden disease or a related syndrome.     

Detailed deletion mapping of chromosome segment 17q12-21 in sporadic breast tumours

Linkage studies have indicated that a gene on chromosome arm 17q, designated BRCAI, confers susceptibility to familial breast and ovarian cancer. To investigate the possible involvement of the BRCAI gene in sporadic breast cancer we have analysed loss of heterozygosity (LOH) in a panel of 100 sporadic primary breast tumours using 10 PCR-based polymorphic markers from 17q12–21. Allele losses were detected in 40 of 100 tumours informative for at least one of the markers analysed. Of these 40 deleted tumours, 27 showed partial or interstitial loss on 17q. The pattern of LOH in the tumours with partial or interstitial LOH revealed three putative distinct deleted regions on 17q12–21. The first lies on the proximal long arm between D17S250 and THRAI; the second one lies between D17S776 and D17S579, the region containing the BRCAI gene; and the third is telomeric to D17S733. The most frequently deleted region overlaps with the minimal region containing the BRCAI gene, suggesting that this gene might also be associated with the development or progression of a proportion of sporadic breast tumours.     

Allelic imbalance in chromosome band 18q21 and SMAD4 mutations in ovarian cancers.

Recently, three candidate tumor suppressor genes, SMAD2 (MADR2/JV18-1), SMAD4 (DPC4), and DCC, were identified in chromosome band 18q21. We examined allelic imbalance (AI) in 18q21 using six polymorphic microsatellite markers in 38 primary ovarian cancers and four ovarian borderline tumors. AI at one or more loci was detected in 15 of 37 (41%) informative ovarian cancers and in none of the four borderline tumors. Frequent AI was detected at the D18S46 (31%) and D18S474 (36%) loci, which were adjacent to the SMAD4 gene, and at the D18S69 (33%) locus, which was telomeric to the DCC gene. Therefore, we searched for mutations of the SMAD4 gene in 42 primary tumors and eight cell lines by PCR-SSCP and sequencing analyses. Missense mutations were detected in two ovarian tumors and three ovarian cancer cell lines, whereas silent mutation was detected in a primary ovarian cancer. These results suggest that there are at least two tumor suppressor genes on chromosome arm 18q and that SMAD4 is of importance in ovarian tumorigenesis.     

Molecular analysis of peritoneal fluid in ovarian cancer patients.

To determine whether genetic abnormalities present in primary ovarian tumors can be used to detect cancer cells in peritoneal fluid, we tested 14 ovarian cancers and 1 benign tumor of the ovary for loss of heterozygosity (LOH) at chromosomal arms 13q, 17p, 17q, and 22q and for mutations in the p53 and K-ras genes. In each case, matched primary tumor, normal tissue, and peritoneal fluid were analyzed. The highest frequency of LOH was found on chromosomal arm 17p (42%), followed by chromosomal arm 17q (36%), 22q (30%), and 13q (21%). Identical alterations were detected in matched peritoneal fluid (either peritoneal wash or ascitic fluid) in 3 of the 8 patients with LOH in the tumor (38%). Direct sequence analysis detected p53 mutations in 3 of the 14 malignant tumors (21%) and no (0) K-ras mutations. Identical mutations were detected in matched peritoneal fluid from all 3 patients with p53 mutations. All 8 of the 14 (57%) malignant tumors that showed at least one genetic abnormality were serous adenocarcinoma and identical alterations were detected in 5 of the 8 (62%) matched peritoneal fluid samples. Our findings indicate that molecular abnormalities can be detected in peritoneal fluid from patients with ovarian cancer and may be used to complement current conventional diagnostic procedures for detection of primary ovarian cancer.     

Defining the region(s) of deletion at 6q16-q22 in human prostate cancer

Deletion of the long arm of chromosome 6 (6q) frequently occurs in many neoplasms, including carcinomas of the prostate and breast and melanoma, suggesting the location of a tumor-suppressor gene or genes at 6q. At present, however, the region of deletion has not been well defined, and the target gene of deletion remains to be identified. In this study, we analyzed 44 primary prostate cancers with 16 polymorphic markers for loss of heterozygosity (LOH) by using PCR-based techniques. We also examined 23 cell lines/xenografts of prostate cancer with 38 markers for LOH by the method of homozygosity mapping of deletion. LOH at 6q16 - q22 was detected in 21 of 44 (48%) primary tumors and in 12 of 23 (52%) cell lines/xenografts. Two regions of LOH were defined. One was 7.5 cM at 6q16 - q21 between markers D6S1716 and D6S1580, and the other was 4.3 cM at 6q22 between D6S261 and D6S1702. Whereas no correlation was found between LOH at 6q16-q22 and patient age at diagnosis or Gleason score, tumors at higher stage appear to have more frequent LOH. These findings suggest that deletion of 6q16 - q22 is a frequent event in prostate cancer, and that the deletion originates from two distinct regions. These results should be useful in identifying the target gene(s) of deletion at 6q.     

Mapping of a new target region of allelic loss to a 2-cM interval at 22q13.1 in primary breast cancer

Allelic losses on chromosome arm 22q are frequently observed in human meningiomas and in carcinomas of the colon, ovary, and breast. Among 140 primary breast cancers we examined for loss of heterozygosity (LOH) at 16 polymorphic loci on the long arm of chromosome 22, 56 (40%) showed LOH for at least one locus. Eleven of these tumors had retained heterozygosity for markers proximal to the NF2 locus but showed LOH for markers distal to NF2. Deletion mapping indicated a new common region of deletion, 2-cM in extent, at q13.1 between Interleukin 2 receptor β (IL2RB) and D22S279. Our results raise the possibility that one or more tumor suppressor genes associated with breast cancer may exist at 22q13.1. Comparison of these results with clinicohistological data indicated that allelic losses on 22q tend to occur more frequently in tumors of malignant histological types. Genes Chromosomes Cancer 21:108–112, 1998. © 1998 Wiley-Liss, Inc.     

Identification of a I-cM region of common deletion on 13q14 associated with human prostate cancer.

Frequent allelic losses on chromosome arm 13q are observed in carcinomas of the head and neck, breast, ovary, and pituitary gland. We analyzed 59 primary prostate tumors (stage B, 18 patients; C, 12 patients; D1, 4 patients; and endocrine therapy-resistant cancer death, 25 patients), as well as 18 metastatic tissues from 14 of the 25 cancer death patients for loss of heterozygosity (LOH) using 35 microsatellite markers on chromosome arm 13q. Of the 59 primary tumors, 31 (53%) showed LOH involving at least one locus. Detailed deletion mapping identified a distinct commonly deleted region in the I-cM interval flanked by D13S153 and D13S273 on 13q14 and this region overlapped a part of the RB1 gene. Paired DNAs were available from both primary and metastatic tumors in the 14 cases of cancer death; among those pairs, we detected LOH on 13q in seven (50%) primary tumors, and in all metastatic foci (P = 0.0029). Moreover, the regions lost in metastatic tissues were more extensive than those seen in the corresponding primary tumors. These results suggest that inactivation of a putative tumor suppressor gene(s) including the RB1 gene on 13q14 plays an important role in human prostate cancer.     

卵巢癌PTEN基因失活机制的探讨

目的　旨在从DNA、mRNA及蛋白水平,探讨卵巢癌PTEN基因的失活机制。方法　48例卵巢癌标本,应用位于染色体10q23 3的4个多态性标记(D10s541、D10s583、D10s1687和D10s2491),采用聚合酶链反应(PCR)及杂合性缺失分析法,检测了PTEN杂合性缺失(LOH);采用聚合酶链反应单链构象多态性分析法(PCR SSCP)检测了PTEN第5、第6、第7和第8外显子的突变;采用逆转录(RT) PCR及免疫组织化学技术检测了PTENmRNA及蛋白的表达。结果　39 6%(19 /48)的卵巢癌存在PTEN基因的LOH, PTEN突变率仅为4 2% (2 /48),PTENmRNA表达缺失率为18 8% (9 /48),蛋白表达缺失率达27 1% (13 /48)。PTEN蛋白表达缺失的病例,LOH的发生率69 2% (9 /13)高于表达阳性者的28 6% (10 /35),差异有统计学意义(P<0 05 )。13例PTEN蛋白表达缺失的病例中,仅有2例( 15 4% )同时有突变和LOH,即存在双等位基因的结构异常; 7例(53 8% )有LOH,其中5例PTENmRNA表达缺失,另2例表达正常; 4例( 30 8% )既无突变也无LOH,其中2例PTENmRNA表达缺失,另2例表达正常。结论　PTEN基因失活在卵巢癌的发病中可能起一定的作用,其失活可能存在多种机制,蛋白表达缺失可能是重要的失活机制。     

Loss of heterozygosity on chromosome 5 in sporadic ovarian carcinoma is a late event and is not associated with mutations in APC at 5q21–22

Frequent loss of heterozygosity in ovarian carcinoma (OC) has been reported on several different chromosomes. We have studied 27 OCs and corresponding normal tissue for loss of heterozygosity (LOH) using 10 markers detecting polymorphisms on chromosome 5 (two on 5p and eight on 5q). Three tumours showed extra copies, rather than loss, of one homologue. Twelve of 24 remaining tumours showed LOH on 5q (50%), and 8 of 21 on 5p (38%). Of the 12 showing LOH on 5q, 7 showed reduction to homozygosity at all informative markers over the chromosome. The remaining 5 showed LOH over all of 5q. These data are consistent with the localisation of a tumour suppressor gene on 5q involved in OC. A good candidate is the APC gene, which is mutated in a number of adenocarcinomas derived from several tissues and is located at 5q21–22. The APC gene was studied in 40 ovarian tumours, including all the OCs showing LOH, by single-strand conformation polymorphism (SSCP). Analysis of all the exons containing published mutations (～4.7 kb of the cDNA) did not reveal any band shifts that could be attributed to mutations. However, a new polymorphism was detected, as well as 7 known polymorphisms. Together, these data indicate that (1) LOH is common on chromosome 5 in OC, (2) APC is not mutated in OC, and (3) another gene (or genes) on chromosome 5q is responsible for the LOH seen. © 1994 Wiley-Liss, Inc.     

Loss of heterozygosity at chromosome regions 22q11–12 and 11p15.5 in renal rhabdoid tumors

Rhabdoid tumors of the kidney are highly malignant neoplasms that occur primarily within the first 3 years of life. Although they are regarded as distinct from Wilms' tumors, their pathogenesis remains unclear. Whereas most cytogenetic studies of these tumors have revealed normal karyotypes, a few reports have indicated abnormalities at chromosome regions 22q and 11p15.5. We analyzed 30 primary renal rhabdoid tumors for loss of heterozygosity (LOH) at both regions and found that 24 of 30 tumors (80%) had LOH at chromosome arm 22q and that 5 of 30 (17%) had LOH at chromosome band 11p15.5. All of the five tumors with LOH at chromosome arm 11p also had LOH at chromosome arm 22q. The data suggest that there is a gene in chromosome 22, probably a tumor suppressor, inactivation of which may be involved in the genesis of renal rhabdoid tumors. A second gene in chromosome segment 11p15.5, in the region of the putative WT2 gene, may also be involved, in at least a subset of rhabdoid tumors. In addition, five tumors were characterized by microsatellite instability at three or more of 21 loci examined, suggesting a possible role for a replicative error in tumorigenesis or progression in some cases of renal rhabdoid tumors. Genes Chromosom Cancer 15:10–17 (1996). © 1996 Wiley-Liss, Inc.     

Evidence for two modes of allelic loss: multifocal analysis on both early and advanced gastric carcinomas

To assess the extent and the timing of allelic loss required for the progression of gastric carcinoma, the intratumoral distribution of loss of heterozygosity (LOH) was compared in early and advanced tumors: early loss is uniformly observed in all tumor areas and late loss is localized in parts of tumor tissue. Tumor sites (167 sites) obtained from 42 gastric carcinoma tissues (26 advanced cancers and 16 early cancers) were examined for LOH on chromosomes 5q, 9p, 13q, 17p, and 18q. By using two or three microsatellite markers for each chromosome arm, it was shown that of 29 tumors showing LOH in at least one tumor site, 15 (51.7%, 12 advanced and three early cancers) harbored multiple losses on three or more chromosome arms, and 89.4% (84 of 94) of these losses was uniformly found in all tumor sites tested. In the remaining 14 tumors (48.3%, eight advanced and six early tumors) with sporadic losses on one or two chromosome arms, 44% (11 of 25) of the losses were commonly shared among the sites tested. Such marked difference (P<0.001, Fisher's exact test) in the intratumoral distribution of multiple and sporadic LOH patterns proposes two distinct LOH subtypes: multiple losses (high LOH), occurring at an early stage with a few additional losses, and sporadic losses (low LOH), taking place relatively late during tumor progression. The multifocal LOH findings imply that, rather than being gradual, the allelic losses take place in two manners that are already determined at an early stage.     

Allelic losses on 18q21 are associated with progression and metastasis in human prostate cancer

We analyzed normal/tumor DNA pairs obtained from 46 patients with prostate cancers (stage B, 16 cases; C, 10 cases; D1, 4 cases; and endocrine therapy-resistant cancer-death, 16 cases) for loss of heterozygosity using 32 microsatellite markers on chromosome 18. Seventeen of the 46 cases (37%) showed loss of heterozygosity (LOH) for at least one locus on the long arm. Detailed deletion mapping in these tumors identified a distinct commonly deleted region within a 5-cM interval on 18q21.1. There was a statistical correlation between the frequency of LOH on 18q and clinical stage (χ² = 12.3; P = 0.0064). LOH on 18q was observed more frequently in Stage D1 cases (4/4; 100%) than in Stage B+C cases (5/26; 19%; P = 0.0046, Fisher's exact test). In 8 of 9 (89%) cancer-death patients from whom DNAs were available from both primary and metastatic tumors, the primary tumors had either no detectable abnormality of chromosome 18 or the region involving loss of heterozygosity was limited while the metastatic foci showed more frequent and extended allelic losses on this chromosome. No abnormalities were detected in the DCC and DPC4 genes when their exons were analyzed separately by single strand conformation polymorphism assay. These results suggest that inactivation of one or more putative tumor suppressor genes on 18q21 other than DCC and DPC4 plays an important role in the progression of human prostate cancer. Genes Chromosomes Cancer 20:140–147, 1997. © 1997 Wiley-Liss, Inc.     

Commonly deleted regions on the long arm of chromosome 21 in differentiated adenocarcinoma of the stomach

During an allelotype analysis of differentiated adenocarcinoma of the stomach, we observed frequent loss of heterozygosity (LOH) on several chromosomes including the long arm of chromosome 21 (21q). Therefore, we analyzed DNA isolated from 45 tumors for LOH at 10 loci on 21q by using polymorphic microsatellite markers. In 20 (44%) of 45 tumors, we detected LOH at single or multiple loci on 21q. Deletion mapping of these 20 tumors revealed two separate commonly deleted regions. Our findings suggest that 21q contains at least two potential tumor suppressor genes which play crucial roles in the development of differentiated adenocarcinoma of the stomach. Genes Chromosom. Cancer 18:318–321, 1997. © 1997 Wiley-Liss, Inc.     

Cutaneous T-cell lymphoma-associated lung cancers show chromosomal aberrations differing from primary lung cancer

Cutaneous T-cell lymphoma (CTCL) patients have an increased risk of certain secondary cancers, the most common of which are lung cancers, especially small cell lung cancer. To reveal the molecular pathogenesis underlying CTCL-associated lung cancer, we analyzed genomic aberrations in CTCL-associated and reference lung cancer samples. DNA derived from microdissected lung cancer cells of five CTCL-associated lung cancers and five reference lung cancers without CTCL association was analyzed by comparative genomic hybridization (CGH). Fluorescent in situ hybridization (FISH), immunohistochemistry (IHC), and loss of heterozygosity (LOH) analysis were performed for selected genes. In CTCL-associated lung cancer, CGH revealed chromosomal aberrations characterizing both lung cancer and CTCL, but also losses of 1p, and 19, and gains of 4q and 7, hallmarks of CTCL. LOH for the CTCL-associated NAV3 gene was detected in two of the four informative primary lung cancers. FISH revealed increased copy number of the KIT gene in 3/4 of CTCL-associated lung cancers and 1/5 of primary lung cancers. PDGFRA and VEGFR2 copy numbers were also increased. IHC showed moderate KIT expression when the gene copy number was increased. CTCL-associated lung cancer shows chromosomal aberrations different from primary lung cancer, especially amplifications of 4q, a chromosome arm frequently deleted in the latter tumor type. Copy numbers and expression of selected genes in chromosome 4 differed between CTCL-associated and reference lung cancers. These preliminary observations warrant further prospective studies to identify the common underlying factors between CTCL and CTCL-associated lung cancer.