Unlike photolysis, the chelated species is not exclusive to iron(III) in order to be degraded. Rather, each strain uniquely consumes varying metal–EDTA complexes through several enzymatic pathways. Agrobacterium radiobacter only degrades Fe(III) EDTA while BNC1 and DSM 9103 are not capable of degrading iron(III) EDTA and are more suited for calcium, barium, magnesium and manganese(II) complexes. EDTA complexes require dissociation before degradation. Alternatives to EDTA
Interest in environmental safety has raised concerns about biodegradability of aminopolycarboxylates such as EDTA. These concerns incentivize the investigation of alternative aminopolycarboxylates. Candidate chelating agents include nitrilotriacetic acid (NTA), iminodisuccinic acid (IDS), polyaspartic acid, S,S-ethylenediamine-N,N′-disuccinic acid (EDDS), methylglycinediacetic acid (MGDA), and L-Glutamic acid N,N-diacetic acid, tetrasodium salt (GLDA). Iminodisuccinic acid (IDS)
Commercially used since 1998, iminodisuccinic acid (IDS) biodegrades by about 80% after only 7 days. IDS binds to calcium exceptionally well and forms stable compounds with other heavy metal ions. In addition to having a lower toxicity after chelation, IDS is degraded by Agrobacterium tumefaciens (BY6), which can be harvested on a large scale. The enzymes involved, IDS epimerase and C−N lyase, do not require any cofactors. Polyaspartic acid
Polyaspartic acid, like IDS, binds to calcium and other heavy metal ions. It has many practical applications including corrosion inhibitors, wastewater additives, and agricultural polymers. A Polyaspartic acid-based laundry detergent was the first laundry detergent in the world to receive the EU flower ecolabel. Calcium binding ability of polyaspartic acid has been exploited for targeting of drug-loaded nanocarriers to bone.
The expression pattern of one or more of these proteins has not yet been found to be of help in distinguishing FHI from other tumor types. Chromosome and gene abnormalities
The EGFR gene which codes for the production of the epidermal growth factor receptor protein is located at band 11.2 on the short (or "p") arm of chromosome 7. Studies using next-generation sequencing targeted to the EGFR gene chromosomal area and confirmed by Sanger sequencing have detected insertion and/or deletion mutations in exon 20 of this gene in the tumor cells of 13 of 13 test FHI cases. While the activity of the normal EGFR protein is blocked by tyrosine kinase inhibitor drugs, most proteins coded by EGFR exon 20-mutated genes do not respond to these drugs due the structural configuration of their EGFR kinase domains; however, certain protein variants coded by these mutated EGFR genes may still be sensitive, and offer a potential treatment option, for a subset of FHI cases. In any event, the identification of these EGFR can help distinguish FHI from other pediatric spindle cell neoplasms with morphologies similar to FHI such as giant cell fibroblastoma.Genomic microarray analyses performed on the two FHI cases with tumors that had areas of sarcoma-like morphology found sarcoma-like cells hyperdiploid (i.e. cell with at least 2 more chromosomes than the normal 48), near tetraploid (i.e.