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Cancer Cells Shed DNA (So Do Normal Cells)

发表于 10-9-2021 11:31:19 | 显示全部楼层 |阅读模式
Allysia Finley, Regulatory Hurdles Block a Cancer Miracle; Illumina's CEO explains the Grail diagnostic test and the FTC action that risks slowing it down. Wall Street Journal, Oct 8, at page A13 (under the heading "Weekend Interiew with Francis deSoza"_.
https://www.wsj.com/articles/reg ... llumina-11633702933


"Scientific breakthroughs are sometimes a matter of serendipity. Eight years ago Meredith Halks-Miller, a pathologist at the genetic-screening company Illumina, stumbled on something unusual while running prenatal blood tests for fetal chromosomal abnormalities. In some blood samples, the fetal genes were normal but the maternal DNA wasn't. Illumina [based in San Diego, Calif] alerted pregnant women's doctors to the finding. After further investigation, all the women were diagnosed with cancer, though none had symptoms when their blood was drawn.  This discovery led to the development of a blood test that can now detect 50 types of cancer * * *

"The Federal Trade Commission last month wrapped up an administrative trial in which it seeks to block Illumina's $8 billion acquisition of Grail, which makes the blood test. Illumina founded Grail in 2015 and spun it off a year later. The Menlo Park, Calif-based start-up is named Grail (from Holy Gail] because scientists have long been on a quest for a blood test that can diagnose cancer early.

"Tumors shed DNA into the blood that signals a cancer's locations. Grail's test scans for these DNA fragments.

"Illumina maintained a 12% stake [after Illumina spub Grail off in . With a commercially viable product nearly in hand, Grail in September 2020 was exploring an initial public offering. That's when Illumina swooped in with its $8 billion offer.

"* * * The Grail test doesn't pick up every cancer, and its sensitivity varies by the type and stage of the disease. But it can detect the 12 deadliest cancers with 60% accuracy. * * *

"Illumina is the leading manufacturer of gene-sequencing machines

"Illumina plans to appeal an adverse FTC ruling [anticipatory, but not handed down yet; besides EU antritrust regulators also want to block the take-over; one objection is enough to block it] in federal court [under federal law, appeal from a federal agency's adverse decision will bre heard in court of appeals, also known as circuit court -- not district court-- which will review law, not facts).

(a) The article is free to nonsubcribers, but there is no need to read it, except quotationds above. There is no need, because the article is a propaganda that Illumina engages against FTC, which obviously bars Illumina to buy the rest of Grail stocks it does not own.
(b) Here is a personal account in her blog site:

Elana Miller, MD (psychiatrist), GRAIL, Inc and the (Not So) Subtle Sexism in Science & Medicine. Zen Psychiatrist, Apr 10, 2021
(critiquing How a Surprising Discovery Turned into a Promising New early-Detection Test for Cancer. Fasr Company (name of a magazine), Apr 1, 2021 AND supplying electronic link to her mother's report: Biamnchi DW et al (Halks-Miller being the last author), Noninvasive Prenatal Testing and Incidental Detection of Occult Maternal Malignancies. JAMA, 314: 162 (2015) ) ​
(i) Elena or Elana is derived from Helen (given name)
(ii) Her mother is
Meredith Halks-Miller, MD
("Board Certified in both Anatomic and Neuropathology")
(iii) Richard Klausner
("was born in 1950/1951. * * * He served as the director of the National Cancer Institute from 1995 to 2001")

(i) Grail's website is not informative at all, so do not go there.
(ii) In 1948, Mandel and Métais described the existence of circulating cell-free DNA (cfDNA) in the blood of healthy individuals -- in French at a France-based journal whoise title might be translated into English as (Nuclear Acids In Human Blood Plasma).
(iii) In 1994, a pair of articles reported cfDNA from cancer in plasma.
(A) Sorenson GD et al, Soluble Normal and Mutated DNA Sequences from Single-Copy Genes in Human Blood. Cancer Epidemiol Biomarkers Prev, 3: 67 (1994).
(B) Vasioukhin V et al, Point Mutations of the N-ras Gene in the Blood Plasma DNA of Patients with Myelodysplastic Syndrome or Acute Myelogenous Leukaemia. Br J Haematol, 86: 774 (1994).

Thus, Halks-Miller's 2015 report was a decade late.
(iv) In a cancer patient, about 1% of cfDNA in plasma is from cancer. Cf DNA is on average 166 base-pair long (ie, very short). The cf DNA from a cancer patient show various errors in DNA duplication. But it is hard to tell (though one may guess) the tissue origin of the cancer.  In other words, each of the following quotations "Tumors shed DNA into the blood that signals a cancer's locations." and Glail's blood test "can detect the 12 deadliest cancers" is false. From abnormal cfDNA, you know the patient has cancers, and start looking in all organs.

(d) Russo A et al, The Molecular Profiling of Solid Tumors by Liquid Biopsy: a Position Paper of the AIOM–SIAPEC-IAP–SIBioC–SIC–SIF Italian Scientific Societies. Cancer Horizons, 6: 100164 (June 1, 2021)


"Highlights: * * * • Despite the evident advantages, liquid biopsy still presents limitations due to both biological and technological issues.

"LB [liquid biopsy] shows some limitations that can be related to both biological and technological issues. Regarding the biological matter, one of the main problems is the risk of ‘false-negative' results that can be due to an extremely limited amount of ctDNA [circulating tumor DNA] in the context of cfDNA ]cell free DNA]. Several factors, such as volume and disease location, seem to affect the concentration of ctDNA, being the metastatic setting associated with higher ctDNA shedding into the bloodstream compared with early-stage disease.

"Almost all human cells release fragments of their genome into body fluids and circulation, following cell apoptosis and necrosis. These cfDNA molecules are stable and maintain the distinctive genetic characteristics of the cells from which they originate. The cfDNA released by apoptosis is much shorter (166-498 kb [kilobasesl which is wrong and should be 'base pairs (bp)']) than that released by necrosis (>10 kb).

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