SCIENCE

Circulating Tumor DNA

ctdna

Cell-free DNA is released by normal cells and cancerous cells into the blood stream and other body fluids. Advanced molecular technologies such as those developed by SAGA Diagnostics are required to distinguish the tumor-derived DNA (“circulating tumor DNA” or ctDNA) from the normal-cell-derived DNA. Recent research indicates ctDNA to be a robust biomarker for tumor burden and that it faithfully represents the genetic defects present in all tumor deposits. Therefore, ctDNA holds great promise for non-invasive monitoring of cancer patients.

The quantity of ctDNA is related to prognosis, and ctDNA analyses can be used to detect actionable and druggable gene mutations as well as resistance mutations at the earliest moment.

Compared to the traditional blood biomarkers and even circulating tumor cells, evidence to date suggests ctDNA to be more sensitive and specific and informative of therapy response earlier than what can be seen by imaging modalities such as CT/MRI scans.

 

IBSAFE™

saga-leader-imageIBSAFE™ is a patent-pending technology for exquisitely sensitive and specific quantification of gene mutations and other sequence variants in DNA or RNA. Error rates plague all methods that employ polymerase enzymes, causing detection noise and false-positives. IBSAFE™ effectively eliminates this error, allowing for an enhanced lower limit of detection down to 0.001%. This is a 10 to 100-fold improvement compared to competing methods such as dPCR, qPCR, or NGS.

  • With IBSAFE™, patients with subclonal mutations may be eligible for targeted therapies.
  • With IBSAFE™, resistance mutations can be detected at the earliest moment.
  • With IBSAFE™, mutant alleles can be quantified in circulating tumor DNA or tissue biopsies.

Inquire regarding in-licensing opportunities within the fields of infectious disease, NIPT, transplant medicine, forensics, and others.

 

 

KROMA™

KROMA™ is a proprietary technology for detection and quantification of tumor-specific chromosomal rearrangements in circulating tumor DNA.

All cancers contain chromosomal rearrangements.

Chromosomal rearrangements are early events in cancer development and thus are “trunk” events and present in most/all cancer subclones. Therefore, tumor-specific chromosomal rearrangements are ideal biomarkers for monitoring cancer patients during therapy to quantify minimal residual disease (MRD), detect occult metastasis, and measure response to therapy. We have shown that KROMA™ can be used to predict poor prognosis in breast cancer and identify metastatic disease up to 3-years prior to patient symptoms.

 

 

Clinical Laboratory Accreditation

The SAGA Diagnostics laboratory is developing an in-house quality assurance system for clinical testing and anticipates ISO 15189:2012 accreditation during 2016-2017.

 

Publications:

  • Winter C, Nilsson MP, Olsson E, George AM, Chen Y, Kvist A, Törngren T, Vallon-Christersson J, Hegardt C, Häkkinen J, Jönsson G, Grabau D, Malmberg M, Kristoffersson U, Rehn M, Gruvberger-Saal SK, Larsson C, Borg Å, Loman N, Saal LH. Targeted exome sequencing of BRCA1 and BRCA2 across a large unselected breast cancer cohort reveals one third of mutations are somatic. Submitted, in revisions.
  • Olsson E, Winter C, George A, Chen Y, Törngren T, Bendahl PO, Borg Å, Gruvberger-Saal SK, Saal LH. Mutation screening of 1237 cancer genes across six model cell lines of basal-like breast cancer. PLOS One. Dec 15 2015: 10(12):e0144528. http://dx.plos.org/10.1371/journal.pone.0144528
  • Tang MH, Dahlgren M, Brueffer C, Tjitrowirjo T, Winter C, Chen Y, Olsson E, Wang K, Törngren T, Sjöström M, Grabau D, Bendahl PO, Rydén L, Niméus E, Saal LH, Borg Å, Gruvberger-Saal SK. Remarkable similarities of chromosomal rearrangements between primary human breast cancers and matched distant metastases as revealed by whole-genome sequencing. Oncotarget. Nov 10 2015: 6(35):37169-84. http://dx.doi.org/10.18632/oncotarget.5951
  • Alkner S, Tang MHE, Brueffer C, Dahlgren M, Chen Y, Olsson E, Winter C, Baker S, Ehinger A, Rydén L, Saal LH, Fernö M, Gruvberger-Saal SK. Contralateral breast cancer can represent a metastatic spread of the first primary tumor. Breast Cancer Research. August 5 2015: 17(1):102. http://www.breast-cancer-research.com/content/pdf/s13058-015-0608-x.pdf
  • Olsson E*, Winter C*, George A, Chen Y, Howlin J, Tang MHE, Dahlgren M, Schulz R, Grabau D, van Westen D, Fernö M, Ingvar C, Rose C, Bendahl PO, Ryden L, Borg Å, Gruvberger-Saal SK, Jernström H, Saal LH. Serial monitoring of circulating tumor DNA in patients with non-metastatic primary breast cancer. EMBO Molecular Medicine. May 18 2015: 7(8):1034-47. http://embomolmed.embopress.org/content/early/2015/05/12/emmm.201404913.full.pdf
  • Saal LH, Vallon-Christersson J, Häkkinen J, Hegardt C, Grabau D, Winter C, Brueffer C, Tang MHE, Reuterswärd C, Schulz R, Karlsson A, Ehinger A, Malina J, Manjer J, Malmberg M, Larsson C, Rydén L, Loman N, Borg Å. The Sweden Cancerome Analysis Network – Breast (SCAN-B) Initiative: a large-scale multicenter infrastructure towards implementation of breast cancer genomic analyses in the clinical routine. Genome Medicine. February 2 2015: 7(1):20. http://genomemedicine.com/content/pdf/s13073-015-0131-9.pdf
  • Saal LH, Gruvberger-Saal SK, Persson C, Lövgren K, Jumppanen M, Staaf J, Jönsson G, Pires MM, Maurer M, Holm K, Koujak S, Subramaniyam S, Vallon-Christersson J, Olsson H, Su T, Memeo L, Ludwig T, Ethier SP, Krogh M, Szabolcs M, Murty VVVS, Isola J, Hibshoosh H, Parsons R, Borg Å. Recurrent gross mutations of the PTEN tumor suppressor gene in breast cancers with deficient DSB repair. Nature Genetics. January 2008: 40(1): 102-7. http://www.nature.com/ng/journal/v40/n1/abs/ng.2007.39.html
  • Saal LH, Johansson P, Holm K, Gruvberger-Saal SK, She Q-B, Maurer M, Koujak S, Ferrando AA, Malmström P, Memeo L, Isola J, Bendahl P-O, Rosen N, Hibshoosh H, Ringnér M, Borg Å, Parsons R. Poor prognosis in carcinoma is associated with a gene expression signature of aberrant PTEN tumor suppressor pathway activity. Proceedings of the National Academy of Sciences USA. May 1 2007: 104(18):7564-9. http://www.pnas.org/content/104/18/7564
  • Saal LH*, Holm K*, Maurer M, Memeo L, Su T, Wang X, Yu JS, Malmstrom PO, Mansukhani M, Enoksson J, Hibshoosh H, Borg A, Parsons R. PIK3CA mutations correlate with hormone receptors, node metastasis, and ERBB2, and are mutually exclusive with PTEN loss in human breast carcinoma. Cancer Research. April 1 2005: 65(7): 2554-2559. http://cancerres.aacrjournals.org/cgi/content/abstract/65/7/2554