C-myc Abnormalities in Non-Hodgkins Lymphoma - A Retrospective Review of Cytogenetic Patterns and Clinical Impact of c-myc Abnormalities by FISH Testing.
Bibliographic record
Abstract
Abstract Recent studies have shown that patients with aggressive histology non-hodgkins lymphoma (NHL) bearing translocations leading to aberrant expression of c-myc have a rapid clinical course and poor outcome, especially when accompanied by translocations involving BCL-2 such as t(14;18). We retrospectively reviewed patients with NHL in which abnormalities of the c-myc gene (rearrangement, extra copies, deletion) were found and correlated the cytogenetic abnormality with presenting characteristics and outcome. Methods: From May 2002 to June 2005, 138 samples were assessed for c-myc; 27 cases of NHL (excluding Burkitt [BL]and BL-like) with c-myc abnormalities were identified and included (25 tissue biopsies, 1 bone marrow, 1 CSF sample). Testing for c-myc abnormalities was initiated for: differential diagnosis of atypical BL or one or more of the following: high MIB-1 index (>70%) − 63%; aggressive morphological features − 81%; aggressive clinical course − 52%; suspected transformation of indolent lymphoma − 19%. Results: There were 12 males and 15 females included with an age range of 26–83 years; 67% had stage 3 or 4 disease and 38% had B-symptoms. The pathological diagnosis was follicular lymphoma (FL) in 3 cases, diffuse large B-cell lymphoma (DLBCL) in 22 cases [13 de novo, 5 transformed from FL, 4 recurrent/refractory] and 2 cases with both FL and DLBCL. FISH analysis for c-myc by the Vysis dual colour break-apart probe (8q24.1) revealed 12 cases with only extra copies (polyploidy) [group 1]; 13 with rearrangement (4 also had extra-copies) [group 2]; one with gene deletion and one with gene deletion and extra-copies. BCL-2 rearrangements were also detected in 22 cases (in group 1, 44%; group 2 69%). All patients were to receive multiagent anthracycline based chemotherapy; chemotherapy was initiated in 89% and one died before this could be given. Thus far, 41% of the patients have died and 19% are alive with refractory disease. The clinical course for group 1 after c-myc abnormality identified was as follows: refractory to chemotherapy - 6 cases, 5 in complete remission (CR), one spontaneous remission without treatment (FL). The median survival for group 1 was 5 months (range 1–21 months) and deaths occurred shortly after current diagnosis (range 1–7 months). The clinical course for group 2 was as follows: refractory to chemotherapy - 11 cases and 3 are currently in a CR. The median survival for group 2 was 9 months (follow-up 1–13 months) and again deaths occurred shortly after current diagnosis (range 1–9 months). Conclusions: Both c-myc gene rearrangement and extra copies of c-myc seem to confer poor prognosis in NHL. Not all patients with c-myc abnormalities have morphological features suggestive of Burkitt-like lymphoma, while some patients with only extra copies of c-myc did have Burkitt-like lymphoma features. Testing for c-myc abnormalities may be indicated not only in patients with aggressive histology but also in those with clinically aggressive patterns of disease, and prospective evaluation of a c-myc testing algorithm to evaluate impact on therapy is required.
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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 | 0.001 |
| 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) | 0.001 | 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".