Abstract LB-89: Germ-line and somatic SMARCA4 mutations characterize small cell carcinoma of the ovary, hypercalcemic type
Bibliographic record
Abstract
Abstract Small-cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is an aggressive tumor and the most common type of undifferentiated ovarian malignancy presenting at less than 40 years of age. Its cause and histogenesis remain unknown. We sequenced the exomes of individuals from three familial cases of SCCOHT. Subsequently, we used whole exome sequencing, Sanger sequencing and immunohistochemistry to analyze germline and tumor DNA from three additional familial cases, 35 non-familial cases and one SCCOHT cell line (BIN-67). DNA sequencing revealed likely deleterious germ-line mutations in the chromatin remodeling gene SMARCA4 in all four familial cases of SCCOHT where DNA was available. This was accompanied by either a somatic mutation or loss of the wild-type allele in the tumor. BIN-67 contained bi-allelic deleterious mutations in SMARCA4. Sequencing of 24 non-familial pathologically-confirmed SCCOHT cases revealed at least one germ-line or somatic likely deleterious SMARCA4 mutation in 22 cases. Immunohistochemical (IHC) analyses of these and an additional 11 tumors showed loss of BRG1 protein in 38/40 cases. Our findings identify alterations in SMARCA4 as a major cause of SCCOHT, which could pave the way for genetic counseling and new treatment approaches. Citation Format: Leora Witkowski, Jian Carrot-Zhang, Steffen Albrecht, Nancy Hamel, Eva Tomiak, David Grynspan, Emmanouil Saloustros, Catherine Gilpin, Rachel Silva-Smith, François Plourde, Barbara Rivera, Ester Castellsagué, Mona Wu, Somayyeh Fahiminiya, Javad Nadaf, Avi Saskin, Madeleine Arseneault, Rouzan G. Karabakhtsian, Elizabeth A. Reilly, Frederick R. Ueland, Anna Margiolaki, Kitty Pavlakis, Sharon M. Castellino, Janez Lamovec, Lawrence M. Roth, Thomas M. Ulbright, Tracey Bender, Michel Longy, Andrew Berchuck, Marc Tischkowitz, Reiner Siebert, Inga Nagel, Vassilis Georgoulias, Colin J.r. Stewart, Glenn McCluggage, Jocelyne Arseneau, Blaise A. Clarke, Yasser Riazalhosseini, Martin Hasselblatt, Jacek Majewski, William D. Foulkes. Germ-line and somatic SMARCA4 mutations characterize small cell carcinoma of the ovary, hypercalcemic type. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-89. doi:10.1158/1538-7445.AM2014-LB-89
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 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) | 0.000 | 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 teacher head, 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".