Comparison of lung adenocarcinoma and squamous cell carcinoma genomes reveals distinct regions of amplification on chromosome 3q
Bibliographic record
Abstract
879 Lung cancer is a leading cause of cancer death worldwide. Non-small cell lung cancer (NSCLC) is the major disease type, with squamous cell carcinoma (SqCC) and adenocarcinoma (AC) as the two main sub-types. SqCC and AC are distinguished by differences in their histopathological and molecular characteristics: SqCC develops more rapidly and is located in the central airways, whereas AC is thought to originate from the epithelium of the lung periphery. Previous findings suggest that, although a similar degree of genetic imbalance exists for AC and SqCC, each type is characterized by a unique pattern of genomic imbalance. Objective: To comprehensively identify the underlying differences in genetic alteration patterns between SqCC and AC, we performed genome-wide tiling resolution array CGH analysis. Novel variations in copy number detected by this high resolution technology may reveal cancer-related loci and will provide potential targets for diagnosis and treatment. Design, Materials and Methods: DNA was isolated from 15 AC cell lines and 9 SqCC cell lines. Sample DNA and a pooled reference genomic DNA sample were differentially labeled and applied to the submegabase resolution tiling-set (SMRT) array for CGH analysis. This array consists of >32,000 overlapping human bacterial artificial chromosome clones that span the entire human genome, allowing true genome-wide assessment of copy number changes for a given sample. SMRT array data was assessed using multiple software applications (SeeGH, weighted frequency, aCGH smooth) and alterations in identified regions are presently be validated by fluorescent in situ hybridization using loci specific probes. Results: In total, 24 whole genome array CGH profiles of lung cancer cell lines were generated. Numerous novel, subtype-specific chromosomal alterations were observed. This included differences of alteration at chromosome arms 2q, 6q, 8q, 9q, 12q, 13q and 16p. Of specific interest were the different locations of chromosomal amplification at 3q in the sub-types. AC showed frequent gains between 3q13 and 3q22 while SqCC displayed a similar frequency at 3q23-3q26. These regions have previously been implicated in lung cancer but not mapped according to sub-type. Further analysis of genes within distinct altered regions will determine if these loci help drive the development of different lung cancer subtypes. Conclusions: Tiling resolution array CGH analysis of AC and SqCC lung cancers revealed both shared and subtype-specific regions of DNA copy aberration, suggesting that differences in tumor genomes help define distinct disease subtypes. Further characterization of the novel aberrations and minimal regions we have identified will implicate additional genes in the two tumorigenesis processes and help tailor disease diagnosis. Supported by NCI SPORE CA 70907, NCI Contract N01-85188 and Genome Canada
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".