| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Regular Articles |
Laboratory of Epithelial Cancer Biology [B. S., S. K. G.], Head and Neck Service [B. S., P. G. S., A. R. S., J. P. S.], Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York 10021; Laboratory of Cancer Biology, Rockefeller University, New York, New York 10021 [A. S.]; and Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030-2399 [P. H. R.]
 |
ABSTRACT |
|---|
 Top ABSTRACT INTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
|
INTRODUCTION |
|---|
|
TopABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
SKY is a novel technique that offers the promise of high-resolution cytogenetics. This method is based on the hybridization of 24 combinatorially labeled painting probes on to metaphase spreads, allowing simultaneous visualization of each chromosome pair by a unique color in a single experiment (6 , 8 , 9) . Given the lack of specificity for precise loci, supplemental analyses are required to refine CGH and SKY findings. FISH follows as an ideal supplemental method for molecular cytogenetic characterization because it allows precise copy number assessment and refinement of chromosomal translocations without the need for additional tissue resources.
In this study, we combined CGH, SKY, and FISH analyses to characterize chromosomal aberrations in a panel of 11 HNSCC cell lines and 1 cell line derived from premalignant oral epithelium. The combination of these techniques identified a complex pattern of aberrations, involving every chromosome. There was a good correlation between the number of abnormalities identified by CGH and SKY, and the studies were confirmatory and complementary in their results. Subsequent FISH analysis allowed a more precise assessment of the CGH-identified amplification at 3q and refinement of unassigned chromosome 3 breakpoints identified by SKY. The combination of molecular cytogenetic techniques used in this study defines a structured paradigm for the identification and refinement of chromosomal aberrations in solid tumors.
|
MATERIALS AND METHODS |
|---|
|
TopABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
CGH.
The DNA from each cell line was labeled using nick translation (Life Technologies, Inc., Rockville, MD) with fluorescein-12-dUTP. As a control, we used DNA extracted from normal placenta and labeled it with Texas red-5-uUTP (New England Nuclear-DuPont, Boston, MA). CGH was performed using previously published methods (6
, 7)
. Then, 7–10 separate metaphases were captured and processed using the Quantitative Image Processing System (Quips Pathvysion System; Applied Imaging, Santa Clara, CA). Red, green, and blue fluorescence intensities were analyzed for all metaphase spreads, normalized to a standard length, and statistically combined to show the red:green signal ratio and 95% confidence intervals for the entire chromosome. Copy number changes were detected based on the variance of the red:green ratio profile from the standard of 1. Ratio values of 1.2 and 2.0 were defined as thresholds for gains and amplifications, respectively, and losses were defined as a ratio value of 0.8 or less.
SKY.
The mixture of human chromosome paints was obtained from ASI (Carlsbad, CA). Hybridization and detection were carried out according to the manufacturer’s protocol with slight modifications (6)
. Chromosomes were counterstained with DAPI. For each case, a minimum of five metaphases was analyzed by SKY. Images were acquired with a SD200 Spectra cube (ASI) mounted on a Nikon Eclipse 800 microscope using a custom-designed optical filter (SKY-1; Chroma Technology, Brattleboro, VT) and analyzed using SKY View 1.2 software (ASI).
Breakpoints on the SKY-painted chromosomes were determined by comparison of corresponding DAPI banding of the same chromosome and by comparison to the G-banded karyotype from the same tumor (4) . A breakpoint was considered recurring if it was identified in two or more cases. A breakpoint cluster was defined as the occurrence of four or more breakpoints on the same chromosomal band.
FISH.
We generated previously a physical map of the region of 3q amplification using 73 YAC clones. The boundaries of 3q amplification were mapped by sequential FISH analysis, identifying an amplification peak contained within three YAC clones.4
FISH was performed as described previously (13)
. In brief, DNA extracted from YAC clones (Research Genetics, Huntsville, AL) was labeled individually by nick translocation using Spectrum green dUTP (Vysis, Downers Grove, IL) and hybridized to the interphase and metaphase spreads from the cell lines. The slides were counterstained with DAPI, and the images were captured using the Quips Pathvysion System (Applied Imaging). To determine the amplification status, 200 individual interphase nuclei and 5 metaphase spreads were analyzed for each cell line. The presence of amplification was accepted if more than 10% of tumor nuclei displayed an increased copy number relative to the chromosome 3 centromeric probe signals and/or tumor ploidy. In cases in which there is a discrepancy between the number of centromeric signals and ploidy, the ploidy number was used to estimate the relative copy number at 3q26.3.
Statistical Analysis.
Statistical comparisons were performed using the JPM software (SAS Institute, Inc., Cary, NC). Pearson correlation coefficient was used to determine the association between the number of structural aberrations identified by SKY and CGH for each cell line.
|
RESULTS |
|---|
|
TopABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
DNA Copy Number Changes Identified by CGH.
DNA extracted from 12 cell lines was subjected to CGH analysis to identify chromosomal gains and losses. Fig. 1a
summarizes the copy number changes identified in the present study. Partial CGH karyotypes from MDA1386 and 1483 showing high-level amplification at 3q are shown in Fig. 2a, A and C
. Underrepresentation of chromosomal regions was noted at 1p, 3p, 4, 8p, 10p, and 18q. The most frequently gained chromosomal regions were 3q, 5p, 8q, 9q, and 14q. High-level amplification was detected at nine chromosomal sites including 3q13, 3q25-q26, 5q22-q23, 7q21, 8q24, 11q13-q14, 12p13, 14q24, and 20q13.1. Recurrent sites of amplification were noted at four sites including 3q25-q26 (42%) in MDA686, MDA886, MDA1186, MDA1386, and 1483; 11q13 (33%) in 584, MDA886, MSK921, and MSK922; 8q24 (17%) in MSK922 and MDA1586; and 9q22-q34 (17%) in MSK922 and MDA1386. Nonrecurrent amplifications were noted at 3q13.3, 7q21, and 12p13 (MDA886); 14q24 (MSK922); and 20q13.1 (MDA1986).
|
|
, respectively.
Analysis of Structural Rearrangements.
A total of 185 translocations, 33 deletions, 4 insertions, and 3 duplications were described in the present study. Recurrent deletions were noted at 3p11, 4q21, 5q13, 9p11, and 12q11. Two reciprocal translocations were noted at t(8;9)(q24;q34) in MSK922 and t(5;11)(q13;q13) in 584. Robertsonian translocations were identified by SKY, involving t(13;13)(q10;q10) in four cell lines (MSK921, MDA1386, 1483, and MDA1986), t(14;14)(q10;q10) in two cell lines (MDA686 and MDA1386), t(14;21)(q10;q10) in 584, t(15;15)(q10;q10) in MDA1186, and t(15;22)(q10;q10) in 1483. Translocations involving the whole chromosomal arm were identified in two cell lines [namely, t(1;13)(q10;q10) in 584 and MSKQLL2, t(3;13)(p10;q10) in MSKQLL2, and t(7;15)(p10;q10) t(10;15) (p10;q10) and t(1;15)(q10;q10) in 584]. Nine isochromosomes were noted, including i(1)(p10) in MSKQLL2; i(2)(p10) in MDA1186; i(3)(q10) in MSK922; i(5)(p10) in MDA686, MDA886, and 1483; i(8)(q10) in 584 and MDA1586; i(9)(q10) in MSK922 and MDA1386; i(10)(p10) in MSK Leuk1; i(10)(q10) in MSK Leuk1; and i(18)(q10) in MDA1986, of which i(5)(p10), i(8)(q10), and i(9)(q10) were recurrent.
Analysis of Breakpoints.
By SKY, 242 breakpoints were identified in rearranged chromosomes, with another 166 breakpoints assigned to chromosomes based on identification of chromosomal segments attached to or inserted into add or der chromosomes but whose specific breakpoints could not be determined. Fig. 1b
summarizes the breakpoints identified by SKY in these cell lines. Overall, recurring breaks (two or more) were noted in 62 sites. Breakpoint clusters (four or more) were seen at 1p11, 1q21, 3p11, 5q11, 5q13, 6q23, 8p11, 8q11, 9p13, 9q13, 10q11, 11q13, 13q10, 14q10, and 15q10 (Fig. 1b)
.
Comparison of CGH and SKY Findings.
A summary of CGH and SKY analyses is presented in Fig. 1
. The median number of copy number changes identified by CGH was 16 (range, 5–29). The median number of aberrations identified by SKY was 19 (range, 7–26). There was a good correlation between the number of structural aberrations identified by SKY and CGH (r = 0.69; P = 0.05).
The combination of these analyses was confirmatory and complementary in the assessment of chromosomal aberrations. SKY helped to define the chromosomal imbalances identified by CGH as detailed in Table 1
. As an example, the genomic imbalances affecting chromosome 9 were identified in six cell lines (MSK921, MSK922, MDA1186, MDA1386, MDA1586, and MDA1986). Whole chromosomal gains identified by CGH coincided with the presence of four copies of der(9) in MDA1986 [der(9) t(1;9) t(p?;p24), der(9) t(3;9)(?;p24), der(9)t(9;10)(p?;q10), and der(9)t(9;11)(q13;q13)], and gains at 9q could be explained by the presence of translocation of 9q to chromosome 8 in MDA1186 and the presence of two normal chromosomes and two additional copies of isochromosome for 9q in MSK922. The CGH ratio profiles from the remaining cell lines showed a loss of 9p and a gain of 9q. These imbalances could be attributed to the presence of i(9)(q10) in MDA1386, two copies of normal chromosome 9 and two copies of del(9)(p11) in MSK921, and two copies of normal chromosome 9 and three copies of translocated 9q [der(4)t(4;9)(q11;q12),der(11) t(9;11) (q13;q10), der(14)t(9;14)(q13;q10), and der(20) t(9;20)] and one copy of der(9)t(9;11)(p11;?)t(X;11)(?;?) in MDA1586.
|
|
, which displays a loss and gain of the short and long arms of chromosome 8, respectively, in MDA1386. Comparable symbiosis was seen in the assessment of amplification events, including refinement of amplification at 11q13-q14 identified by CGH in four cases (584, MDA886, MSK921, and MSK922). In the majority of cases, the amplification resulted from translocation of chromosomal material from this region to the other chromosomes in the genome, with the exception of MSK922, where a duplication of the 11q13-q14 region was identified.
The true strength of the combination of SKY and CGH analyses was observed in the refinement of complex rearrangements. As an example, the gain of 7q11-q32, including amplification at 7q21 in MDA886, resulted from the presence of a complex marker chromosome consisting of chromosomes 3, 5, 7, and 10 and two additional copies of translocated 7q chromosome material to chromosome 5.
Moreover, several chromosomal abnormalities were uniquely identified by either CGH or SKY. As an example, amplification at 11q13 and 12p13 in MDA886 was only visible by CGH. Conversely, isochromosomes at i(1)(p10) and i(5)(p10) identified by SKY in MSKQLL2 and 1483, respectively, were not detected in the corresponding CGH profiles. These discrepancies may be due to a low prevalence of these clones in the tumor genome leading to a lack of detection by CGH or sampling limitations by SKY. In addition, in MSK Leuk1, SKY identified i(10)(p10) and i(10)(q10), but CGH could not detect any imbalance on chromosome 10. This assessment highlights the limitation of CGH analysis in detecting balanced abnormalities because there was no apparent loss or gain of DNA sequences from chromosome 10 in this cell line.
Refinement of 3q Amplification by FISH.
The combination of CGH and SKY was insufficient to precisely define several subtle chromosomal aberrations. To illustrate the utility of FISH as a supplementary approach, an analysis of 3q aberrations was performed. Amplification at 3q was identified in 42% of the cell lines in this study, and gains were identified in 25% of the cell lines in this study. The chromosomal derivation of 3q overrepresentation in these cell lines identified by CGH included duplications, insertions, and complex translocations, as defined by SKY (Table 2)
. High-level amplification of chromosome 3 at the 3q26-q29 region coincided with translocated material from chromosome 3q in MDA686, MDA886, MDA1186, MDA1386, and 1483 (Table 2)
. In MDA886, 3q26.1-q26.3 amplification results from translocation of chromosome 3q material to chromosomes 2 and 5 and an additional copy of 3q. In the MDA1386 cell line, the amplicon was derived from the translocation of 3q material to chromosomes 2 and 17 and duplication of the 3q25-q26 region (Fig. 2b)
. However, the quantification of the extent of amplification was not discernible, and precise 3q breakpoints could not be defined by SKY analysis.'
|
. In cases with high-level amplification, 6–12 copies were identified by FISH using the YAC probe (Fig. 2a, B and D)
, compared with 4–5 copies in cell lines with gain of 3q and 1–4 copies in cell lines with no gain or amplification detected by CGH. A discrepancy was seen in the number of FISH signals between interphase nuclei and metaphase spreads from the cell lines MDA886 and 1483, which can be attributed to the presence of multiple clones and the number of copies of der(3) chromosomes. Similarly, discrepancies between the number of 3q centromeric signals and tumor ploidy in two cases could be attributed to the presence of duplicated chromosome der(3).
Unassigned chromosome 3 breakpoints identified by SKY were refined as shown in Table 2
. As an example, a duplication of 3q in cell line MDA1386 and an insertion of chromosome 3 material into chromosome 2 in MSK922 were noted by SKY. FISH analysis identified the precise breakpoint in both cell lines, identifying the origin of the duplication and insertion as 3q26.3 in MDA1386 (Fig. 2b, C)
. In addition, in cell line 1483, we identified a der(3)t(3;14)(q26
q27;?) by SKY, but FISH analysis identified this as a cryptic duplication at 3q26.3 on the der(3) (Fig. 2c, C)
.
|
DISCUSSION |
|---|
|
TopABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
CGH analysis showed that HNSCCs tend to be more complex genetically than many solid tumors, with a median of 16 copy number changes/case compared with 13 copy number changes/case for lung cancer and 5.6 copy number changes/case for colorectal carcinoma (14 , 15) . In contrast, cell lines derived from pancreatic and breast cancers tend to be more complex, having a median of 21.6 and 19.6 copy number changes/case, respectively (16 , 17) . Although more complex, the pattern of aberrations identified by CGH analysis of HNSCC cell lines is similar to that reported for primary cancers by other groups, with loss of 1p, 3p, 4, 8p, 10p, and 18q and gain of 3q, 5p, 8q, 9q, and 14q (10, 11, 12) . Nine independent sites of amplification were identified, of which amplifications at 3q (42%) and 11q13 (33%) were the most common. Although there was significant overlap between the copy number changes identified by CGH and those reported by conventional cytogenetic analysis, notable differences in the detection of gains and amplification were present, including aberrations at 3q and 5p (2, 3, 4, 5) .
SKY analysis identified several recurrent translocations and novel breakpoints. On the basis of our previous G-banding analysis of clonally abnormal karyotypes of primary tumor and cell lines, we have identified recurrent breakpoints at 1p13, 3p13-p23, 3q, 4q, 5q, 6q15, 8p, 8q, 10q, 12p11.2, 18q, and 19q (2) . The pattern of recurrent breakpoints identified in the present study by SKY is comparable with those seen by G-banding. The most common recurrent chromosomal rearrangements identified by SKY were i(5)(p10) in three cases, i(8)(q10) and i(9)(q10) in two cases each, and whole arm translocations involving chromosome 1, 3, 7, 10, 13, 14, 15, and 21. Interestingly, Jin et al. (4) , in a cytogenetic study of 105 HNSCCs, reported similar recurrent translocations involving the entire chromosomal arm. SKY enhanced the chromosomal assessment by detecting recurrent complex interchromosomal rearrangements such as t(5;14)(?;p10) in three cases, t(10;15)(q11;p10) in two cases, and t(2;16)(?;?q24) in two cases.
CGH and SKY analyses were overlapping and complementary in their assessment of individual chromosomal aberrations. There was a good correlation (r = 0.69) between the absolute number of aberrations detected by CGH and SKY. This is similar to the findings in two prior studies (16 , 18) on breast and pancreatic carcinomas that have also shown a high level of concordance between these techniques. The study by Kytölä et al. (16) reported a high level of correlation (r = 0.70) between the absolute number of aberrations identified by CGH and SKY in 15 breast cancer cell lines. Ghadimi et al. (18) reported similar findings in pancreatic cancers. Recent studies have measured genomic instability by either CGH or SKY and correlated it with the presence of p53, Ku80, and/or XRCC4 aberrations (17 , 19 , 20) . Given the high level of concordance, the data suggest that the independent use of either SKY or CGH is sufficient for genomic instability analysis. The p53 status of nine of the cell lines in this study was published previously, with mutations identified in three cases (21) . Interestingly, there was no correlation between the number of aberrations detected by CGH or SKY and the p53 status. This may reflect the advanced genomic composition of the HNSCC cell lines.
Gain of genetic information at 3q has been identified in a diverse group of malignancies but shows the highest prevalence in carcinomas of mucosal origin, including those originating from the head and neck, cervix, lung, and esophagus (10
, 22, 23, 24)
. The minimal common region of chromosomal involvement identified by CGH is identical in all tumor types involving the 3q26-q27 region. We have narrowed the region of peak amplification to three nonchimeric YAC clones by FISH.4
Moreover, we identified 3q amplification as an important transition event and independent prognostic marker in HNSCC.5
In this study, we confirmed the presence of a high-level amplification at 3q26 probe by FISH. In addition, we were able to refine unassigned breakpoints on chromosome 3 by SKY. We screened the YAC clones used in the FISH analysis by PCR for the presence of candidate genes using gene-specific primers. Only the presence of PIK3CA was demonstrated in the YAC clones, which was also found to be overexpressed by Western blot analysis.4 PIK3CA encodes for the p110
catalytic subunit of phosphatidylinositol 3'-kinase, which has oncogenic potential and has been shown to be amplified and overexpressed in ovarian and cervix cancers (25
, 26)
. Combined, these data suggest that PIK3CA is a strong candidate oncogene in HNSCC. In addition, our work has also shown similar results in squamous cell carcinoma of the lung.4
The results reported here demonstrate the individual and combined strengths of novel molecular cytogenetic technologies, namely, the ability to characterize copy number changes, amplifications, and the derivation of each rearranged chromosomal segment. The combination of CGH, SKY, and FISH analyses enabled us to identify and refine copy number changes and new recurrent sites of rearrangements. These analyses represent important starting points for genetic characterization and gene discovery.
|
ACKNOWLEDGMENTS |
|---|
|
FOOTNOTES |
|---|
1 Supported in part by the Young Investigator Award from the American Society of Clinical Oncology, the Bryne Fund, and the Faculty Research Fellowship from the American College of Surgeons (all to B. S.). 
2 To whom requests for reprints should be addressed, at Laboratory of Epithelial Cancer Biology, Head and Neck Service, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021. Phone: (212) 639-2024; Fax: (212) 717-3302; E-mail: singhb{at}mskcc.org
3 The abbreviations used are: HNSCC, head and neck squamous cell carcinoma; CGH, comparative genomic hybridization; SKY, spectral karyotyping; FISH, fluorescence in situ hybridization; YAC, yeast artificial chromosome; DAPI, 4',6-diamidino-2-phenylindole; ASI, Applied Spectral Imaging.
5 B. Singh, S. Gogineni, A. Stoffel, A. Poluri, D. G. Pfister, A. Shaha, A. Patak, G. Bosl, C. Cordon-Cardo, J. P. Shah, and P. H. Rao. Impact of 3q amplification on tumor progression and clinical outcome in patients with head and neck cancer, submitted for publication.
Received 10/12/00. Accepted 3/28/01.
|
REFERENCES |
|---|
|
TopABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
This article has been cited by other articles:
|
|
 |
|
  S. Ocak, M. L. Sos, R. K. Thomas, and P. P. Massion High-throughput molecular analysis in lung cancer: insights into biology and potential clinical applications Eur. Respir. J., August 1, 2009; 34(2): 489 - 506. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. W. Chan, C. J. Lim, L. S. Loo, Y. F. Chong, C. Huang, and W. Hong TEADs Mediate Nuclear Retention of TAZ to Promote Oncogenic Transformation J. Biol. Chem., May 22, 2009; 284(21): 14347 - 14358. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Y. Kim, C. C. Bommelje, B. E. Lee, Y. Yonekawa, L. Choi, L. G. Morris, G. Huang, A. Kaufman, R. J. H. Ryan, B. Hao, et al. SCCRO (DCUN1D1) Is an Essential Component of the E3 Complex for Neddylation J. Biol. Chem., November 28, 2008; 283(48): 33211 - 33220. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. O-charoenrat, I. Sarkaria, S. G. Talbot, P. Reddy, S. Dao, I. Ngai, A. Shaha, D. Kraus, J. Shah, V. Rusch, et al. SCCRO (DCUN1D1) Induces Extracellular Matrix Invasion by Activating Matrix Metalloproteinase 2 Clin. Cancer Res., November 1, 2008; 14(21): 6780 - 6789. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. H. Rao, D. Roberts, Y.-J. Zhao, D. Bell, C. P. Harris, R. S. Weber, and A. K. El-Naggar Deletion of 1p32-p36 Is the Most Frequent Genetic Change and Poor Prognostic Marker in Adenoid Cystic Carcinoma of the Salivary Glands Clin. Cancer Res., August 15, 2008; 14(16): 5181 - 5187. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Petrovic, R. H. Costa, L. F. Lau, P. Raychaudhuri, and A. L. Tyner FoxM1 Regulates Growth Factor-induced Expression of Kinase-interacting Stathmin (KIS) to Promote Cell Cycle Progression J. Biol. Chem., January 4, 2008; 283(1): 453 - 460. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Pelosi, B. Del Curto, M. Trubia, A. G. Nicholson, M. Manzotti, G. Veronesi, L. Spaggiari, P. Maisonneuve, F. Pasini, A. Terzi, et al. 3q26 Amplification and Polysomy of Chromosome 3 in Squamous Cell Lesions of the Lung: A Fluorescence In situ Hybridization Study Clin. Cancer Res., April 1, 2007; 13(7): 1995 - 2004. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Sarkaria, P. O-charoenrat, S. G. Talbot, P. G. Reddy, I. Ngai, E. Maghami, K. N. Patel, B. Lee, Y. Yonekawa, M. Dudas, et al. Squamous Cell Carcinoma Related Oncogene/DCUN1D1 Is Highly Conserved and Activated by Amplification in Squamous Cell Carcinomas Cancer Res., October 1, 2006; 66(19): 9437 - 9444. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. L. Rothschild, A. H. Shim, A. G. Ammer, L. C. Kelley, K. B. Irby, J. A. Head, L. Chen, M. Varella-Garcia, P. G. Sacks, B. Frederick, et al. Cortactin Overexpression Regulates Actin-Related Protein 2/3 Complex Activity, Motility, and Invasion in Carcinomas with Chromosome 11q13 Amplification Cancer Res., August 15, 2006; 66(16): 8017 - 8025. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Jung, R. Kindich, J. Kamradt, M. Jung, M. Muller, W. A. Schulz, R. Engers, G. Unteregger, M. Stockle, R. Zimmermann, et al. Genomic and Expression Analysis of the 3q25-q26 Amplification Unit Reveals TLOC1/SEC62 as a Probable Target Gene in Prostate Cancer Mol. Cancer Res., March 1, 2006; 4(3): 169 - 176. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. J.C. Slebos, Y. Yi, K. Ely, J. Carter, A. Evjen, X. Zhang, Y. Shyr, B. M. Murphy, A. J. Cmelak, B. B. Burkey, et al. Gene Expression Differences Associated with Human Papillomavirus Status in Head and Neck Squamous Cell Carcinoma Clin. Cancer Res., February 1, 2006; 12(3): 701 - 709. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. S. Sarkaria, D. Pham, R. A. Ghossein, S. G. Talbot, M. Hezel, M. E. Dudas, M. I. Ebright, S. Chuai, N. Memoli, E. S. Venkatraman, et al. SCCRO Expression Correlates With Invasive Progression in Bronchioloalveolar Carcinoma Ann. Thorac. Surg., November 1, 2004; 78(5): 1734 - 1741. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. B. Wreesmann, W. Shi, H. T. Thaler, A. Poluri, D. H. Kraus, D. Pfister, A. R. Shaha, J. P. Shah, P. H. Rao, and B. Singh Identification of Novel Prognosticators of Outcome in Squamous Cell Carcinoma of the Head and Neck J. Clin. Oncol., October 1, 2004; 22(19): 3965 - 3972. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. O-charoenrat, V. Rusch, S. G. Talbot, I. Sarkaria, A. Viale, N. Socci, I. Ngai, P. Rao, and B. Singh Casein Kinase II Alpha Subunit and C1-Inhibitor Are Independent Predictors of Outcome in Patients with Squamous Cell Carcinoma of the Lung Clin. Cancer Res., September 1, 2004; 10(17): 5792 - 5803. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. G. Masayesva, P. Ha, E. Garrett-Mayer, T. Pilkington, R. Mao, J. Pevsner, T. Speed, N. Benoit, C.-S. Moon, D. Sidransky, et al. Gene expression alterations over large chromosomal regions in cancers include multiple genes unrelated to malignant progression PNAS, June 8, 2004; 101(23): 8715 - 8720. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. B. Wreesmann, E. M. Sieczka, N. D. Socci, M. Hezel, T. J. Belbin, G. Childs, S. G. Patel, K. N. Patel, G. Tallini, M. Prystowsky, et al. Genome-Wide Profiling of Papillary Thyroid Cancer Identifies MUC1 as an Independent Prognostic Marker Cancer Res., June 1, 2004; 64(11): 3780 - 3789. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Overholtzer, P. H. Rao, R. Favis, X.-Y. Lu, M. B. Elowitz, F. Barany, M. Ladanyi, R. Gorlick, and A. J. Levine The presence of p53 mutations in human osteosarcomas correlates with high levels of genomic instability PNAS, September 30, 2003; 100(20): 11547 - 11552. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. L. Estilo, P. O-charoenrat, I. Ngai, S. G. Patel, P. G. Reddy, S. Dao, A. R. Shaha, D. H. Kraus, J. O. Boyle, R. J. Wong, et al. The Role of Novel Oncogenes Squamous Cell Carcinoma-related Oncogene and Phosphatidylinositol 3-Kinase p110{alpha} in Squamous Cell Carcinoma of the Oral Tongue Clin. Cancer Res., June 1, 2003; 9(6): 2300 - 2306. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Dai, W.-G. Zhu, C. D. Morrison, R. M. Brena, D. J. Smiraglia, A. Raval, Y.-Z. Wu, L. J. Rush, P. Ross, J. R. Molina, et al. A comprehensive search for DNA amplification in lung cancer identifies inhibitors of apoptosis cIAP1 and cIAP2 as candidate oncogenes Hum. Mol. Genet., April 1, 2003; 12(7): 791 - 801. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. I. Kutler, A. D. Auerbach, J. Satagopan, P. F. Giampietro, S. D. Batish, A. G. Huvos, A. Goberdhan, J. P. Shah, and B. Singh High Incidence of Head and Neck Squamous Cell Carcinoma in Patients With Fanconi Anemia Arch Otolaryngol Head Neck Surg, January 1, 2003; 129(1): 106 - 112. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. B. Wreesmann, R. A. Ghossein, S. G. Patel, C. P. Harris, E. A. Schnaser, A. R. Shaha, R. M. Tuttle, J. P. Shah, P. H. Rao, and B. Singh Genome-Wide Appraisal of Thyroid Cancer Progression Am. J. Pathol., November 1, 2002; 161(5): 1549 - 1556. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Singh, A. Stoffel, S. Gogineni, A. Poluri, D. G. Pfister, A. R. Shaha, A. Pathak, G. Bosl, C. Cordon-Cardo, J. P. Shah, et al. Amplification of the 3q26.3 Locus Is Associated with Progression to Invasive Cancer and Is a Negative Prognostic Factor in Head and Neck Squamous Cell Carcinomas Am. J. Pathol., August 1, 2002; 161(2): 365 - 371. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Fujii, T. Dracheva, A. Player, S. Chacko, R. Clifford, R. L. Strausberg, K. Buetow, N. Azumi, W. D. Travis, and J. Jen A Preliminary Transcriptome Map of Non-Small Cell Lung Cancer Cancer Res., June 1, 2002; 62(12): 3340 - 3346. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Singh, P. G. Reddy, A. Goberdhan, C. Walsh, S. Dao, I. Ngai, T. C. Chou, P. O-charoenrat, A. J. Levine, P. H. Rao, et al. p53 regulates cell survival by inhibiting PIK3CA in squamous cell carcinomas Genes & Dev., April 15, 2002; 16(8): 984 - 993. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
